Transient naming deficits associated with insular lesions in a patient with encephalitis.

We describe a patient with acute herpes simplex encephalitis with left-hemispheric hippocampal, parahippocampal and insular lesions. Although prototypic language areas were unaffected, the patient suffered from an inability to name objects or animals displayed on pictures. This deficit was transient and gradually disappeared 8 weeks after the initial diagnosis. Our findings are in line with a previous report showing similar deficits in a patient with a comparable lesion pattern and support the hypothesis that left insular lesions can produce severe naming deficits. Using FDG-PET we ruled out that functional deactivation in classical language areas account for the observed naming deficits.

Burden of herpes simplex virus encephalitis in the United States.

Herpes simplex virus encephalitis (HSVE) is a disease of public health concern, but its burden on the healthcare of United States has not been adequately assessed recently. We aimed to define the incidence, complications and outcomes of HSVE in the recent decade by analyzing data from a nationally representative database. Healthcare Cost and Utilization Project databases were utilized to identify patients with primary discharge diagnosis of HSVE. Annual hospitalization rate was estimated and several preselected inpatient complications were identified. Regression analyses were used to identify mortality predictors. Key epidemiological factors were compared with those from other countries. Total 4871 patients of HSVE were included in our study. The annual hospitalization rate was 10.3 ± 2.2 cases/million in neonates, 2.4 ± 0.3 cases/million in children and 6.4 ± 0.4 cases/million in adults. Median age was 57 years and male:female incidence ratio was 1:1. Rates of some central nervous system complications were seizures (38.4%), status epilepticus (5.5%), acute respiratory failure (20.1%), ischemic stroke (5.6%) and intracranial hemorrhage (2.7%), all of which were significantly associated with mortality. In-hospital mortality in neonates, children and adults were 6.9, 1.2 and 7.7%, respectively. HSVE still remains a potentially lethal infectious disease with high morbidity and mortality. Most recent epidemiological data in this study may help understanding this public health disease, and the patient outcome data may have prognostic significance.

N-methyl-d-aspartate receptor autoimmunity affects cognitive performance in herpes simplex encephalitis.

OBJECTIVES: To investigate the prevalence and temporal development of N-methyl-d-aspartate receptor (NMDAR) autoantibodies in relation to neurocognitive performance in patients with herpes simplex encephalitis (HSE). METHODS: This prospective observational study enrolled a total of 49 HSE patients within a randomized controlled trial of valacyclovir. Cerebrospinal fluid and serum samples were drawn in the initial stage of disease, after 2 to 3 weeks and after 3 months. Anti-NMDAR IgG was detected with HEK293 cells transfected with plasmids encoding the NMDA NR1 type glutamate receptor. A batch of neurocognitive tests, including the Mattis Dementia Rating Scale (MDRS), Glasgow Coma Scale (GCS), Reaction Level Scale (RLS85), Mini-Mental State Examination (MMSE) and National Institutes of Health (NIH) stroke scale, was performed during 24 months' follow-up. RESULTS: Anti-NMDAR IgG was detected in 12 of 49 participants. None were antibody positive in the initial stage of disease. In ten of 12 positive cases, specific antibodies were detectable only after 3 months. Notably, the development of NMDAR autoantibodies was associated with significantly impaired recovery of neurocognitive performance. After 24 months' follow-up, the median increase in MDRS total score was 1.5 vs. 10 points in antibody-positive and -negative participants (p=0.018). CONCLUSIONS: Anti-NMDAR autoimmunity is a common complication to HSE that develops within 3 months after onset of disease. The association to impaired neurocognitive recovery could have therapeutical implications, as central nervous system autoimmunity is potentially responsive to immunotherapy.

Impoverished descriptions of familiar routes in three cases of hippocampal/medial temporal lobe amnesia.

Recent research has challenged classic theories of hippocampal function in spatial memory with findings that the hippocampus may be necessary for detailed representations of environments learned long ago, but not for remembering the gist or schematic aspects that are sufficient for navigating within those environments (Rosenbaum et al., 2000; Rosenbaum, Winocur, Binns, & Moscovitch, 2012). We aimed to probe further distinctions between detailed and schematic representations of familiar environments in three cases of hippocampal/medial temporal lobe (MTL) amnesia by testing them on a route description task and mental navigation tasks that assess the identity and location of landmarks, and distances and directions between them. The amnesic cases could describe basic directions along known, imagined routes, estimate distance and direction between well-known landmarks, and produce sketch maps with accurate layouts, suggestive of intact schematic representations. However, findings that their route descriptions lack richness of detail, along with impoverished sketch maps and poor landmark recognition, substantiates previous findings that detailed representations are hippocampus-dependent.

Psychiatric aspects of herpes simplex encephalitis, tick-borne encephalitis and herpes zoster encephalitis among immunocompetent patients.

The psychopathological symptoms occurring in the course of diseases associated with infections are often initially isolated and non-characteristic, and may cause diagnostic difficulties. Moreover, such disorders tend to be less responsive to psychiatric management. Among possible causes such as trauma, neoplasm and vascular changes, inflammatory changes of the brain as a result of a viral infection should also be considered. There were 452 registered cases of viral encephalitis in Poland in 2010, and although not very prevalent they remain a severe and life-threatening condition. What is more, the frequently occurring neurological and psychiatric complications of viral encephalitis often result in permanent disabilities, causing a significant decrease in the quality of life. This article presents the three types of encephalitis that are most prevalent among immunocompetent patients in Poland, i.e. herpes simplex encephalitis (HSE), tick-borne encephalitis (TBE) and herpes zoster encephalitis (HZE). The psychopathology of the acute phase of the infection, the residual symptoms, features apparent in imaging studies and some neuropathological aspects are also presented. The paper also focuses on psychiatric aspects of the diagnostics and treatment of the described conditions. The clinical pictures of these infections are quite specific, although they cover a wide range of symptoms, and these characteristic features are described. The aim of this review is also to show the significance of thorough diagnostics and a multidisciplinary approach to patients with viral CNS infections.

Self-perspective inhibition deficits cannot be explained by general executive control difficulties.

Understanding other people's point of view is crucial for successful social interaction but can be particularly challenging in situations where the other person's point view conflicts with our own view. Such situations require executive control processes that help us resist interference from our own perspective. In this study, we examined how domain-general these executive processes are. We report the performance of two pairs of brain-damaged patients who had sustained lesions in different areas of the prefrontal cortex and who showed deficits in classic executive function tasks. The patients were presented with desire reasoning tasks in which two sources of executive control were manipulated: the need to resist interference from one's own desire when inferring someone else's conflicting desire and the need to resist interference from the ascription of an approach motivation when inferring an avoidance-desire. The pattern of performance of the two pairs of patients conformed to a classic double dissociation with one pair of patients showing a deficit in resisting interference from their own perspective but not from the ascription of an approach motivation while the other pair of patients showed the opposite profile. The results are discussed in relation to the specificity of the processes recruited when we resist interference from our own perspective.

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.

Persistence of feelings and sentience after bilateral damage of the insula.

It has been convincingly established, over the past decade, that the human insular cortices are involved in processing both body feelings (such as pain) and feelings of emotion. Recently, however, an interpretation of this finding has emerged suggesting that the insular cortices are the necessary and sufficient platform for human feelings, in effect, the sole neural source of feeling experiences. In this study, we investigate this proposal in a patient whose insular cortices were destroyed bilaterally as a result of Herpes simplex encephalitis. The fact that all aspects of feeling were intact indicates that the proposal is problematic. The signals used to assemble the neural substrates of feelings hail from different sectors of the body and are conveyed by neural and humoral pathways to complex and topographically organized nuclei of the brain stem, prior to being conveyed again to cerebral cortices in the somatosensory, insular, and cingulate regions. We suggest that the neural substrate of feeling states is to be found first subcortically and then secondarily repeated at cortical level. The subcortical level would ensure basic feeling states while the cortical level would largely relate feeling states to cognitive processes such as decision-making and imagination.

Numeracy skills in patients with degenerative disorders and focal brain lesions: a neuropsychological investigation.

OBJECTIVE: To characterize the numerical profile of patients with acquired brain disorders. METHOD: We investigated numeracy skills in 76 participants--40 healthy controls and 36 patients with neurodegenerative disorders (Alzheimer dementia, frontotemporal dementia, semantic dementia, progressive aphasia) and with focal brain lesions affecting parietal, frontal, and temporal areas as in herpes simplex encephalitis (HSE). All patients were tested with the same comprehensive battery of paper-and-pencil and computerized tasks assessing numerical abilities and calculation. Degenerative and HSE patients also performed nonnumerical semantic tasks. RESULTS: Our results, based on nonparametric group statistics as well as on the analysis of individual patients, and all highly significant, show that: (a) all patients, including those with parietal lesions--a key brain area for numeracy processing--had intact processing of number quantity; (b) patients with impaired semantic knowledge had much better preserved numerical knowledge; and (c) most patients showed impaired calculation skills, with the exception of most semantic dementia and HSE patients. CONCLUSION: Our results allow us, for the first time, to characterize the numeracy skills in patients with a variety of neurological conditions and to suggest that the pattern of numerical performance can vary considerably across different neurological populations. Moreover, the selective sparing of calculation skills in most semantic dementia and HSE suggest that numerical abilities are an independent component of the semantic system. Finally, our data suggest that, besides the parietal areas, other brain regions might be critical to the understanding and processing of numerical concepts.

Herpes encephalitis during natalizumab treatment in multiple sclerosis.

In this case report we describe the first non-fatal herpes simplex virus encephalitis (HSE) case with natalizumab for multiple sclerosis (MS). A 36-year-old woman, previously treated with immunomodulatory and immunosuppressive drugs for MS, developed acute encephalitis after 6 monthly natalizumab perfusions. Brain imaging demonstrated suggestive bi-temporal lesions. Herpes simplex virus type-1 DNA was detected in cerebrospinal fluid. The patient improved gradually after a 21-day course of intravenous acyclovir, but neuropsychiatric changes remained 5 months later. Our non-fatal case of HSE and other reported cases of herpes infections provide evidence of an increased risk with natalizumab and point to the need for clinicians to maintain awareness.

A common processing system for the concepts of artifacts and actions? Evidence from a case of a disproportionate conceptual impairment for living things.

We report the results of a single-case study carried out with a brain-damaged patient, G.C., whose conceptual knowledge of living things (animals and plants) was significantly more impaired than his knowledge of artifacts and his knowledge of actions, which were similarly impaired. We examined whether this pattern of conceptual impairment could be accounted for by the "sensory/functional" or the "manipulability" account for category-specific conceptual impairments advocated within the feature-based organization theory. To this end, we assessed, first, the patient's knowledge of sensory compared to functional and motor features and, second, his knowledge of nonmanipulable compared to manipulable items. The findings showed that the patient's disproportionate impairment for living things compared to both artifacts and actions was not associated with a disproportionate impairment of sensory compared to functional or motor knowledge or with a relative sparing of manipulable compared to nonmanipulable items. We then discuss how alternative theories of conceptual knowledge organization could account for G.C.'s pattern of category-specific deficit.

Using SenseCam with an amnesic patient: accessing inaccessible everyday memories.

Forgetting is a normal and everyday occurrence that may sometimes reflect a complete loss of the mnemonic record or a failure to encode it in the first place. However, on many occasions with the help of cues we can eventually or suddenly recall a memory that seemed to be lost, thus highlighting the probability that many instances of "forgetting" may in fact reflect inaccessibility rather than true loss. We report here on our amnesic patient CR who presents an extreme example of this normal everyday forgetting. For 4 weeks, CR recorded regular personal autobiographical events both on a SenseCam (henceforth SC) and in a written diary form. Subjective and objective aspects of recall were measured each weekend both without any cues and then with either a SC or diary cue. We show that the SC enabled CR to recall significantly more detailed episodic memories than reading the diary and importantly we observed that the qualitative nature of these memories was different. We comment on the considerable potential of SC for therapeutic purposes.

Progressive gray matter loss and changes in cognitive functioning associated with exposure to herpes simplex virus 1 in schizophrenia: a longitudinal study.

OBJECTIVE: Longitudinal changes in gray matter volume and cognitive performance were evaluated among individuals exposed to neurotropic herpes simplex virus subtype 1 (HSV1). There is a replicable association of HSV1 exposure with smaller prefrontal volumes and cognitive impairments in schizophrenia. METHOD: The authors concurrently examined the whole-brain longitudinal trajectory over 1 year of gray matter volumes and executive functioning measured with the Wisconsin Card Sorting Test among 26 first-episode antipsychotic-naive subjects with schizophrenia and 38 healthy subjects. Age, gender, socioeconomic status, and exposure to cytomegalovirus (another virus of the herpes family that was previously associated with cognitive impairments) were the covariates. RESULTS: Significant gray matter loss in the posterior cingulate gyrus was noted among the HSV1-seropositive schizophrenia subjects over 1 year but not among other groups. Prefrontal gray matter volumes did not show longitudinal changes. Binomial mixed-effects models indicated that improvement over 1 year in Wisconsin Card Sorting Test categories completed and perseverative errors occurred in significantly fewer HSV1-seropositive schizophrenia subjects than in the HSV1-seronegative schizophrenia subjects or the healthy subjects regardless of serological status. Three-way interactions of diagnosis, HSV1 status, and time were significant for both categories completed and perseverative errors. An increase in perseverative errors over 1 year, but not the change in the number of categories completed, correlated with longitudinal volume loss of the posterior cingulate gyrus. CONCLUSIONS: These observations suggest that HSV1 exposure may be associated with longitudinal gray matter loss in the posterior cingulate gyrus and decline in executive functioning among subjects with schizophrenia.

Cognitive representation of orientation: a case study.

Although object orientation in the human brain has been discussed extensively in the literature, the nature of the underlying cognitive representation(s) remains uncertain. We investigated orientation perception in BC, a patient with bilateral occipital and parietal damage from a herpes encephalitis infection. Our results show that in addition to general inaccuracy in discriminating and reproducing line orientations, her errors take the form of left-right mirror reflections across a vertical coordinate axis. We propose that in BC, the cognitive impairment is in failing to represent the direction of tilt for line orientations. Our results suggest that there exists a level of representation in the human brain at which line orientations are represented compositionally, such that the direction of a line orientation's tilt from a vertical mental reference meridian is coded independently of the magnitude of its angular displacement. Reflection errors across a vertical axis were observed both in visual and tactile line orientation tasks, demonstrating that these errors arise at a supra-modal level of representation not restricted to vision, or, alternatively, that visual-like representations are being constructed from the tactile input.

Neuropsychologic outcomes in children with neonatal herpes encephalitis.

Neonatal herpes simplex virus infection with involvement of the central nervous system is a serious disease with high morbidity, even with acyclovir therapy. The disability includes cerebral palsy and different aspects of cognitive dysfunction which are of utmost importance for the child's future habilitation. We conducted a descriptive cohort study to define neuropsychologic outcomes and determine the relationship between neonatal neuroimaging and neuropsychologic outcomes. Among 267,690 children born in the Stockholm area over 12 years (1989-2000), 14 were diagnosed with neonatal herpes including central nervous system involvement. Nine children were neuropsychologically evaluated. Neonatal herpes virus infection had an even greater impact on cognitive function, speech ability, and attention deficit than anticipated. Relapse leading to deterioration was demonstrated in one child. Social skills were influenced to a lesser degree. Neurodevelopmental outcomes of the children were not well-correlated with extent of cerebral damage as visualized by computed tomography at 7-28 days after onset of signs. Neuropsychologic assessment is essential in the habilitation of the child, and a prerequisite for the evaluation of new treatments and for the assessment of deterioration of cerebral function related to relapses.