'A disease that makes criminals': encephalitis lethargica (EL) in children, mental deficiency, and the 1927 Mental Deficiency Act.

Encephalitis lethargica (EL) was an epidemic that spread throughout Europe and North America during the 1920s. Although it could affect both children and adults alike, there were a strange series of chronic symptoms that exclusively affected its younger victims: behavioural disorders which could include criminal propensities. In Britain, which had passed the Mental Deficiency Act in 1913, the concept of mental deficiency was well understood when EL appeared. However, EL defied some of the basic precepts of mental deficiency to such an extent that amendments were made to the Mental Deficiency Act in 1927. I examine how clinicians approached the sequelae of EL in children during the 1920s, and how their work and the social problem that these children posed eventually led to changes in the legal definition of mental deficiency. EL serves as an example of how diseases are not only framed by the society they emerge in, but can also help to frame and change existing concepts within that same society.

Sleep and behavior during vesicular stomatitis virus induced encephalitis in BALB/cJ and C57BL/6J mice.

Intranasal application of vesicular stomatitis virus (VSV) produces a well-characterized model of viral encephalitis in mice. Within one day post-infection (PI), VSV travels to the olfactory bulb and, over the course of 7 days, it infects regions and tracts extending into the brainstem followed by clearance and recovery in most mice by PI day 14 (PI 14). Infectious diseases are commonly accompanied by excessive sleepiness; thus, sleep is considered a component of the acute phase response to infection. In this project, we studied the relationship between sleep and VSV infection using C57BL/6 (B6) and BALB/c mice. Mice were implanted with transmitters for recording EEG, activity and temperature by telemetry. After uninterrupted baseline recordings were collected for 2 days, each animal was infected intranasally with a single low dose of VSV (5×10(4) PFU). Sleep was recorded for 15 consecutive days and analyzed on PI 0, 1, 3, 5, 7, 10, and 14. Compared to baseline, amounts of non-rapid eye movement sleep (NREM) were increased in B6 mice during the dark period of PI 1-5, whereas rapid eye movement sleep (REM) was significantly reduced during the light periods of PI 0-14. In contrast, BALB/c mice showed significantly fewer changes in NREM and REM. These data demonstrate sleep architecture is differentially altered in these mouse strains and suggests that, in B6 mice, VSV can alter sleep before virus progresses into brain regions that control sleep.

The opsoclonus­myoclonus syndrome.

The opsoclonus­myoclonus syndrome is a rare and distinct neurological disorder characterised by rapid multidirectional conjugate eye movements (opsoclonus), myoclonus and ataxia, along with behavioural changes in adults and irritability in children. Sometimes it is due to a self-limiting presumed para-infectious brainstem encephalitis but it may also represent a non-metastatic manifestation of neuroblastoma in children and small cell carcinoma of the lung in adults. In this article, we will describe the clinical features, diagnosis, pathogenesis and management.

Personality changes after Toscana virus (TOSV) encephalitis in a 49-year-old man: A case report.

Toscana virus (TOSV) infection may often cause symptomatic meningitides and encephalitides. These usually subside in few days and their sequelae do not last for more than few weeks. We here report the case of a 49-year-old man who developed encephalitis after being bitten by phlebotomi in a region near southern Tuscany, where TOSV is endemic, and who developed postencephalitic seizures and subsequently, persistent personality alterations, characterized by sexually dissolute behavior and aggressiveness. One year after infection, the patient needs a combination of an SSRI antidepressant and a mood stabilizer/anticonvulsant to obtain less than optimal symptom improvement. This points to the need of establishing better preventive measures in Tuscany and nearby regions.

Interferon-alpha causes neuronal dysfunction in encephalitis.

Interferon-alpha (IFNalpha) is a pleomorphic cytokine produced by nucleated cells in response to viral infection. In patients, treatment with IFNalpha has side effects including cognitive impairment resembling subcortical dementia, which is a hallmark of human immunodeficiency virus (HIV)-associated dementia (HAD). IFNalpha is increased in the CSF of HAD patients compared with HIV patients without dementia. In this study, blocking IFNalpha in a HIV encephalitis (HIVE) mouse model with intraperitoneal injections of IFNalpha neutralizing antibodies (NAbs) significantly improved cognitive function compared with untreated or control antibody-treated HIVE mice during water radial arm maze behavioral testing. Treatment with IFNalpha NAbs significantly decreased microgliosis and prevented loss of dendritic arborization in the brains of HIVE mice. Furthermore, treatment of primary neuron cultures with IFNalpha resulted in dose-dependent loss of dendritic arborization that was blocked with IFNalpha NAb treatment and partially blocked with NMDA antagonists [AP5 and MK801 (dizocilpine maleate)] indicating glutamate signaling is involved in IFNalpha-mediated neuronal damage. These results show that IFNalpha has a major role in the pathogenesis of HIVE in mice and is likely important in the development neurocognitive dysfunction in humans with HIV. Blocking IFNalpha could be important in improving cognitive and pathological developments in HAD patients and may be clinically important in other neuroinflammatory diseases as well.

Impairment of short-term memory and Korsakoff syndrome are common in AIDS patients with cytomegalovirus encephalitis.

BACKGROUND AND PURPOSE: The diagnosis of cytomegalovirus encephalitis (CMV-E) in AIDS patients is challenging as other illnesses may obscure the symptoms. Here, we characterize the clinical symptoms of CMV-E and link them to post-mortem findings. Patients and methods In 254 homosexual men with AIDS, followed from HIV diagnosis to death before the antiretroviral combination therapy era, CMV-E was suspected in 93 cases. All were CMV-positive in blood. Neurological examination, including cognitive testing was performed in 34 of them within 6 months before death. CMV-E was diagnosed by CMV-PCR in cerebrospinal fluid (n = 24) or by post-mortem (n = 24). RESULTS: The majority complained of forgetfulness (91%), balance difficulties (85%) and impotence (85%). Impaired short-term memory was present in 29 patients. It was extreme in 17, justifying the diagnosis of Korsakoff's syndrome. This was often associated with infectious CMV in blood (P = 0.01). Brainstem symptoms were found in 19 patients. Post-mortem examination often revealed ventriculoencephalitis. CMV was found primarily around the ventricles and in other structures, described in Korsakoff's syndrome. CONCLUSION: The location of CMV in the brain corresponded well to the clinical findings, demonstrating the close relationship between the neurological symptoms and the neuroanatomical lesions.

Structure and function in acquired prosopagnosia: lessons from a series of 10 patients with brain damage.

Acquired prosopagnosia varies in both behavioural manifestations and the location and extent of underlying lesions. We studied 10 patients with adult-onset lesions on a battery of face-processing tests. Using signal detection methods, we found that discriminative power for the familiarity of famous faces was most reduced by bilateral occipitotemporal lesions that involved the fusiform gyri, and better preserved with unilateral right-sided lesions. Tests of perception of facial structural configuration showed severe deficits with lesions that included the right fusiform gyrus, whether unilateral or bilateral. This deficit was most consistent for eye configuration, with some patients performing normally for mouth configuration. Patients with anterior temporal lesions had better configuration perception, though at least one patient showed a more subtle failure to integrate configural data from different facial regions. Facial imagery, an index of facial memories, was severely impaired by bilateral lesions that included the right anterior temporal lobe and marginally impaired by fusiform lesions alone; unilateral right fusiform lesions tended to spare imagery for facial features. These findings suggest that (I) prosopagnosia is more severe with bilateral than unilateral lesions, indicating a minor contribution of the left hemisphere to face recognition, (2) perception of facial configuration critically involves the right fusiform gyrus and (3) access to facial memories is most disrupted by bilateral lesions that also include the right anterior temporal lobe. This supports assertions that more apperceptive variants of prosopagnosia are linked to fusiform damage, whereas more associative variants are linked to anterior temporal damage. Next, we found that behavioural indices of covert recognition correlated with measures of overt familiarity, consistent with theories that covert behaviour emerges from the output of damaged neural networks, rather than alternative pathways. Finally, to probe the face specificity of the prosopagnosic defect, we tested recognition of fruits and vegetables: While face specificity was not found in most of our patients, the data of one patient suggested that this may be possible with more focal lesions of the right fusiform gyrus.

Neuropsychological sequelae of acute-onset sporadic viral encephalitis.

Acute encephalitis is an inflammation of the brain parenchyma. In the USA, by estimation, 20,000 cases occur every year. A variety of cognitive deficits may persist after the acute stage, and they are often the sole cause of disability. Recent literature demonstrates the heterogeneity of both amnestic disorders and the outcome following encephalitis. Herpes simplex virus is the most commonly recognised single aetiology of sporadic encephalitis and it may be the cause of the most severe symptoms. Antiviral medication, however, seems to have improved the cognitive outcome when compared to the historical, untreated cases. The cognitive sequelae following herpes simplex virus encephalitis (HSVE) are best known and most commonly described, e.g., in textbooks, but they do not represent the typical symptomatology of encephalitis in general. Much less is unfortunately known about other types of encephalitis, those that account perhaps up to 80% of all cases, where both mild and severe defects have been observed. This article summarises the current knowledge.

Neurodevelopment and cognition in children after enterovirus 71 infection.

BACKGROUND: Enterovirus 71 is a common cause of hand, foot, and mouth disease and encephalitis in Asia and elsewhere. The long-term neurologic and psychiatric effects of this viral infection on the central nervous system (CNS) are not well understood. METHODS: We conducted long-term follow-up of 142 children after enterovirus 71 infection with CNS involvement - 61 who had aseptic meningitis, 53 who had severe CNS involvement, and 28 who had cardiopulmonary failure after CNS involvement. At a median follow-up of 2.9 years (range, 1.0 to 7.4) after infection, the children received physical and neurologic examinations. We administered the Denver Developmental Screening Test (DDST II) to children 6 years of age or younger and the Wechsler intelligence test to children 4 years of age or older. RESULTS: Nine of the 16 patients with a poliomyelitis-like syndrome (56%) and 1 of the 5 patients with encephalomyelitis (20%) had sequelae involving limb weakness and atrophy. Eighteen of the 28 patients with cardiopulmonary failure after CNS involvement (64%) had limb weakness and atrophy, 17 (61%) required tube feeding, and 16 (57%) required ventilator support. Among patients who underwent DDST II assessment, delayed neurodevelopment was found in only 1 of 20 patients (5%) with severe CNS involvement and in 21 of 28 patients (75%) with cardiopulmonary failure (P<0.001 for the overall comparison). Children with cardiopulmonary failure after CNS involvement scored lower on intelligence tests than did children with CNS involvement alone (P=0.003). CONCLUSIONS: Enterovirus 71 infection with CNS involvement and cardiopulmonary failure may be associated with neurologic sequelae, delayed neurodevelopment, and reduced cognitive functioning. Children with CNS involvement without cardiopulmonary failure did well on neurodevelopment tests. (ClinicalTrials.gov number, NCT00172393 [ClinicalTrials.gov].).

Psychiatric symptoms and cognitive dysfunction caused by Epstein-Barr virus-induced encephalitis.

Epstein-Barr virus (EBV) encephalitis is rare and shows a wide range of clinical manifestations. We report an immunocompromised patient with EBV encephalitis diagnosed by EBV-specific PCR and antibody testing in the cerebrospinal fluid who presented with psychiatric symptoms and cognitive dysfunction in the absence of any neurological impairments or infectious signs. Clinical recovery and clearance of cerebrospinal fluid EBV DNA appeared following ganciclovir treatment within 6 weeks.

Rodent model systems for studies of HIV-1 associated dementia.

Understanding of HIV-1 neuropathogenesis and development of rationale therapeutic approaches requires relevant animal models. The putative mechanisms of neuroinflammatory and neurotoxic events triggered by HIV-1 brain infection are reflected by a number of rodent models. These include transgenic animals (either expressing viral proteins or pro-inflammatory factors), infection with murine retroviruses, and severe combined immunodeficient (SCID) mice reconstituted with human lymphocytes and injected intracerebrally with HIV-1-infected human monocyte-derived macrophages. The potential importance and limitations of the models in reflecting human disease are discussed with emphasis on their utility for development of therapies to combat HIV-1-associated neurologic impairment.

[Acute non-herpetic viral encephalitis of juvenile onset: analysis of 11 cases based on initial clinical symptoms].

We investigated clinical features of juvenile patients presenting non-herpetic viral acute encephalitis (4 men and 7 women, aged of onset; 23.7 +/- 3.3 years) without malignancy and immunodeficiency. We divided the patients into two groups according to initial neurological symptoms: psychiatric symptoms mimicking schizophrenia (group P, n=5), seizure (group S, n=6), and compared clinical manifestations among the two groups. Symptoms frequently seen in initial phase of the illness were neck stiffness (4 cases, 36%), involuntary movement (7 cases, 64%) and convulsion (8 cases, 73%). There were no significant difference among the groups except seizure. Patients in group P had more CSF cells and CSF lymphocytes compared with other groups (p < 0.05 and p < 0.01, respectively). Abnormal intensities in T2-weighted magnetic resonance images were found in 4 cases (36%). The term from the onset to leaving hospital of group P (213 +/- 227 days) was longer than that of group S (98 +/- 85 days), although it did not reach a significant difference. These findings indicate that juvenile acute non-herpetic encephalitis initially presenting psychiatric symptoms was serious and had relatively poor prognosis.

Preferring one taste over another without recognizing either.

Stimuli can be discriminated without being consciously perceived and can be preferred without being remembered. Here we report a subject with a previously unknown dissociation of abilities: a strong behavioral preference for the taste of sugar over saline, despite a complete failure of recognition. The pattern of brain damage responsible for the dissociation suggests that reliable behavioral choice among tastes can occur in the absence of the gustatory cortex necessary for taste recognition.

Selective memory impairment for personally familiar colors following encephalitis.

A 19-year-old man presented with a peculiar memory impairment following non-herpetic viral encephalitis. He was exclusively impaired in generating images for colors of possessions previously well known to him, and consequently these seemed less familiar. He appeared unable to access personally familiar and autobiographical color attributes. Single-photon emission computed tomography and electroencephalogram findings suggest that the right-sided functional abnormalities, specifically in the frontal and temporal regions, were implicated as the functional locus for the patient's unique problem.

Frecuencia de signos y síntomas neuropsiquiátricos en pacientes con encefalitis viral / Frequency of neuropsychiatric signs and symptoms in patients with viral encephalitis

Introducción. La encefalitis viral aguda (EVA) es un padecimiento frecuente que suele cursar con alteraciones psiquiátricas, que han sido estudiadas de forma sistemática. Objetivo. Conocer la frecuencia y la evolución de las manifestaciones neuropsiquiátricas en pacientes con EVA. Pacientes y métodos. Se ha realizado un estudio retrospectivo. Se definió la EVA como un padecimiento agudo y de curso progresivo en sujetos previamente sanos, con signos clínicos de alteración difusa del sistema nervioso central, electroencefalograma anormal y/o líquido cefalorraquídeo (LCR) inflamatorio. Excluimos a los pacientes con epilepsia previa o serología positiva para el virus de la inmunodeficiencia humana (VIH), y los casos compatibles con encefalitis herpética por datos electroencefalográficos o de imagen con focalización hacia las regiones temporales o frontales, o con prueba de ADN positiva para herpes en el LCR. Se incluyeron 83 pacientes. Se registraron los signos y síntomas psiquiátricos manifestados durante la fase aguda y un año después del alta hospitalaria (secuelas). Resultados. Las alteraciones psiquiátricas en la fase aguda fueron: agitación psicomotora (67%), somnolencia (55%), desorientación (47%), alucinaciones visuales (43%) y agresividad (34%). Un año después de la hospitalización, en 70 pacientes en control clínico, encontramos: alteraciones de la memoria (16%), agresividad (9%), afasia (8%), alucinaciones visuales (8%) y alucinaciones auditivas (7%). La mortalidad fue del 6%. Conclusiones. Las alteraciones neuropsiquiátricas son muy frecuentes durante la fase aguda de la encefalitis viral, lo que es relevante para el diagnóstico diferencial de los pacientes que acuden a los servicios de urgencias con alteraciones conductuales. A un año del alta, las principales secuelas son neuropsiquiátricas, y predomina el déficit cognitivo (AU)

Introduction. Acute viral encephalitis (AVE) is a frequent condition that usually courses with psychiatric alterations but few systematic studies have been conducted to investigate it. Aims. To determine the frequency and the progression of the neuropsychiatric symptoms in patients with AVE. Patients and methods. A retrospective study was carried out. AVE was defined as an acute and progressively coursing condition in previously healthy subjects, with clinical signs of diffuse alteration of the central nervous system, abnormal electroencephalogram and/or inflammatory cerebrospinal fluid (CSF). We excluded patients who previously had epilepsy, a positive serodiagnosis for human immunodeficiency virus (HIV), and cases compatible with herpes simplex encephalitis from electroencephalographic or imaging data with focalisation towards temporal, frontal, regions or a positive DNA test for herpes in CSF. Finally, 83 patients were included. The psychiatric signs and symptoms that were produced were recorded during the acute phase and one year after discharge from hospital (sequelae). Results. The psychiatric disorders in the acute phase were psychomotor agitation (67%), drowsiness (55%), disorientation (47%), visual hallucinations (43%) and aggressiveness (34%). One year after hospitalisation, in a sample of 70 patients in a clinical control, we found memory disorders (16%), aggressiveness (9%), aphasia (8%), visual hallucinations (8%), and auditory hallucinations (7%). The mortality rate was 6%. Conclusions. Neuropsychiatric disorders are very frequent during the acute phase of viral encephalitis, which is relevant for the differential diagnosis in patients who visit emergency departments with behavioural disorders. One year after hospital discharge, the main sequelae are of a neuropsychiatric nature and cognitive impairment is predominant (AU)

Neuropsychiatric sequelae of Nipah virus encephalitis.

The authors followed nine patients with Nipah virus encephalitis over the course of 24 months. Eight of the nine developed psychiatric features assigned to the encephalitis. Three patients developed major depressive disorder immediately after recovering from the encephalitis, and two developed depression approximately 1 year after the outbreak. Two patients developed personality changes, and two suffered chronic fatigue syndrome. Neuropsychological testing was accomplished in eight of the nine patients. Deficits in attention, verbal, and/or visual memory were substantial in seven of the eight patients tested. Verbal memory was more impaired than visual memory in these patients. Comparison between psychiatric and cognitive impairment and total number of brain lesions showed no discernible trends.

[The mild encephalitis-hypothesis--new findings and studies]. / Die milde Enzephalitishypothese--neue Befunde und Studien.

Causes and pathogenesis of psychiatric disorders is poorly understood. Infections by viruses or other agents may disturb neurotransmitters and elicit behavioral abnormalities, and induce long lasting immune reactions, referred to as mild encephalitis (ME). New findings (pathology, biochemistry, imaging) in schizophrenia and bipolar psychoses are compatible with ME hypothesis. In Chorea Sydenham and PANDAS syndrome autoimmune ME seems to explain anxiety-compulsive-hyperactivity symptoms. Add-on-therapy with Cox-II-blockers or valacyclovir improved acute schizophrenia, CSF filtration some cases of therapy resistant psychoses.

[Two cases of acute encephalitis/encephalopathy associated with adenovirus type 3 infection].

Although adenovirus type 3 is a common pathogen of pediatric infection, there have been few reports on encephalitis and encephalopathy caused by this virus. We report two cases, one of acute encephalitis and another of transient encephalopathy, associated with adenovirus type 3 infection. Case 1, an 11-year-old boy with unconsciousness and convulsions, was diagnosed as having acute encephalitis because adenovirus type 3 was isolated from the cerebrospinal fluid. Case 2, a 3-year-old boy with intermittent excitement and hallucinations, was diagnosed as having transient encephalopathy. MRI, EEG, and cerebrospinal fluid studies were normal. Our cases and previously reported cases exhibit a wide clinico-pathological spectrum of the central nervous system involvement by adenovirus type 3.

[An adult case suspected of recurrent measles encephalitis with psychiatric symptoms].

An adult case of suspected recurrent measles encephalitis with psychiatric symptoms is reported. A 46-year-old woman developed measles encephalitis presenting as schizophreniform disorder and recovered three months after onset. However, approximately two years later, she suffered a relapse of encephalitis presenting with psychiatric symptoms (auditory hallucination, cenesthopathy, insomnia, depressive mood) and became comatose. Following ten days of symptomatic treatment, her clinical symptoms gradually improved. Three months later, she made a remarkable recovery without neurological sequelae. Since then, she has maintained good condition for six years. The diagnosis of suspected recurrent measles encephalitis was made on the basis of the change of anti-measles IgM antibody titers. Acute relapse of disseminated encephalomyelitis (ARDEM) and multiple sclerosis (MS) were ruled out due to no abnormal finding of cerebral white matter on MRI. Six years after the recurrent episode, the titers of anti-measles IgM antibodies (EIA) in the serum were still high, suggesting that she was suffering from a chronic measles virus infection. This patient should be followed up for a longer time because there is a possibility that she might be in the latent period of subacute sclerosing panencephalitis (SSPE).