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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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The opsoclonus–myoclonus 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.

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 (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.

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.

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.

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.

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].)., (Copyright 2007 Massachusetts Medical Society.)

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.

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.

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.

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.

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.

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.

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.

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.

This article describes an inpatient case treated at the Mental Hospital in Zurawica, in which an appearance of a viral (herpetic?) encephalitis was preceded by a paranoid syndrome. One of many clinical situations, when an appearance of a somatic disease was preceded by manifestation of psychic disturbances, was demonstrated in this article.

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).

Background: Herpes simplex encephalitis is one of the most common and serious sporadic encephalitides of immunocompetent adults. Herpes simplex virus 2 (HSV-2) infections of the central nervous system usually manifest as subacute encephalitis, recurrent meningitis, myelitis, and forms resembling psychiatric syndromes., Objectives: To report and discuss magnetic resonance imaging (MRI) findings and clinical features in atypical brainstem encephalitis and facial palsy associated with HSV-2., Setting: Neurology department of a tertiary referral center., Patient: A 37-year-old woman was admitted to the hospital with fever, diplopia, left hemiparesis, sensory change in the face and limbs, personality changes, frontal dysexecutive syndrome, and a stiff neck. Brain MRI showed multifocal high-signal intensities in the pons, midbrain, and frontal lobe white matter on T2-weighted and fluid-attenuated inversion recovery images. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) amplification analysis was positive for HSV-2. Acyclovir therapy was started, and the encephalitic symptoms disappeared with a negative conversion of HSV-2 PCR in the CSF. However, after the discontinuation of acyclovir therapy, peripheral facial palsy occurred on the left side. A possible relapse or delayed manifestation of the HSV-2 infection was suspected, and the acyclovir therapy was restarted. A complete remission was achieved 3 days after the treatment. She was discharged without any neurologic sequelae., Conclusions: We describe a patient who developed atypical encephalitis due to HSV-2 and peripheral facial palsy, which could also be related to the HSV-2. This case suggests that HSV-2 should be considered among the possible causes of atypical or brainstem encephalitis and that the PCR amplification method of the CSF can help reveal the possible cause of HSV-2.

Introduction: Mutism is absence of verbal expression with conservation of language comprehension. The origin of mutism is multifactorial and may followed from cranial trauma surgery of the posterior fossa, acquired epileptic syndromes and psychogenic origin., Objective: To refer patients who had presented mutism of diverse etiology., Clinical Cases: We analysed three children who had presented mutism originated by diverse causes. Case 1. A child with family and school problems, attention deficits and limited communication resources. Neurological examination and other auxiliary test (EEG) were normal. He presented no alteration in language or speech. We recommended the change of the school and a psychotherapeutic orientation. Case 2. A 4 year old female child who has suffered varicella 15 days earlier and presented limitations in her verbal expression despite maintain her linguistically capacity. She showed a indifferent behavior and her movements were without finality. Neurological examination was normal. The girl understood and followed instruction properly. However her verbal communication was absent. Total recuperation occurred in 72 hours. Case 3. A 12 years old child who had suffered a cranial traumatism with loss of consciousness ten days earlier. After this traumatism, he presented behavior changes, disorientation and blurred vision. Additionally he presented stereotypies and limitations in psychosocial connections. Despite his mutism, he conserved the structure and content of language. SPECT showed hypoperfusion in orbitotemporal region. Improvement was total 20 days after his traumatism., Conclusions: The mutism has multifactorial etiology. References were made to three cases who's mutism was related to emotional causes, post-varicella complications and posttraumatic events.

Declarative memory depends on the hippocampus and related medial temporal lobe and diencephalic structures. Declarative memory has usually been found to be available to conscious recollection. A recent study (Chun and Phelps, Nat Neurosci 1999;2:844-847) found that damage to the medial temporal lobe (including the hippocampus) impaired performance on a perceptual learning task, yet the learning was accomplished in the absence of memory for the stimuli. This finding raised the possibility that some hippocampus-dependent tasks may be inaccessible to awareness and may be performed without evoking conscious memory processes. Using the same task, we show that when damage is confined largely to the hippocampal formation, perceptual learning is intact. Thus, the available data suggest that damage limited to the hippocampal formation does not impair nonconscious (nondeclarative) memory. Further, the data do not contradict the idea that hippocampus dependent memory is accessible to conscious recollection. Finally, perceptual learning was impaired in patients, with extensive damage to the medial temporal lobe and with additional variable damage to lateral temporal cortex.

Epstein-Barr virus encephalitis is a self-limiting disease with few sequelae. Persistence of neurologic deficits prior to and after the acute illness has yet to be described in children. We describe five children with persistent cognitive and focal neurologic deficits due to chronic Epstein-Barr virus encephalitis with various T2-weighted magnetic resonance imaging abnormalities. Clinical features were a 9-year-old boy with aphasia and apraxia, an 11-year-old girl with impulsivity and inappropriate behavior, a 17-year-old boy with deterioration of cognitive skills and judgment, a 5-year-old boy with complex-partial seizures, and a 6-year-old girl with obsessive-compulsive behavior. All patients had elevated serum Epstein-Barr virus titers for acute infection, with cerebrospinal fluid polymerase chain reaction positive for Epstein-Barr virus in four patients. Three children were treated with methylprednisolone with minimal improvement without changes on magnetic resonance imaging. Epstein-Barr virus encephalitis can present with chronic and insidious neurologic symptoms and should be considered in the differential diagnosis of children with acute or chronic neurologic illness of unknown etiology.

Two patients with severe global amnesia are described who differ in the extent to which they have acquired new semantic information. Patient SS, who has extensive medial temporal lobe damage including the hippocampus as well as surrounding cortical areas, has failed to acquire virtually any new information regarding vocabulary or famous faces that entered the public domain since the onset of his amnesia. In contrast, patient PS, who has a selective lesion of the hippocampus proper, has gained a sense of familiarity of novel vocabulary and famous people, even though her effortful retrieval of this new semantic knowledge remains impaired. These findings extend to amnesia of adult onset, the proposal of Vargha-Khadem and colleagues that in patients with selective hippocampal injury, cortical areas surrounding the hippocampus may play an important role in new semantic learning [Vargha-Khadem, F., Gadian, D.G., Watkins, K. E., Connelly, A., Van Paesschen, W. and Mishkin, M., regarding the importance of the subhippocampal cortices in the mediation of new semantic learning in children with hippocampal lesions, Science, 1997, 277, 376-380].

Virusencephalitis is characterised by clinical symptoms of a parenchymatous inflammation. In addition, early mental status changes often occur as a result of virusencephalitis, beside focal neurological deficiencies, epileptic seizures, cerebral compression, even coma. Other pathological manifestations of virusencephalitis are disturbances of the neurohumoral and the endocrine system, which are often recognised and treated too late. This case report describes symptoms, treatment, and complications of a 76 year old female in-patient, who was diagnosed with virusencephalitis. The number of lymphocytes in the cerebrospinal fluid was increased to 30 cells per microliter, liquor albumin was 1705 mg/l, liquor sugar was 53 mg/dl and liquor lactat was 1.9 mmol/l. IgM antibodies against herpes viruses were found in the cerebrospinal fluid and distinct contrasting foci were found near the mammillary bodies, hypothalamus, tractus opticus, hypophyseal stalk and right parahippocampal in the magnetic resonance imaging of the head, indicating a focal herpes simplex encephalitis. Within seven days, the following symptoms developed: akinetic parkinsonian syndrome, central diabetes insipidus with hypernatremia and polyuria (6 l/die), hypothyreosis, adrenal insufficiency with adynamia, sopor, hypotension and even hypophyseal coma. Panhypopituitarism was diagnosed after measuring the basal hormone levels (ACTH, TSH, FT3, FT4, Cortisol, Prolactin, LH, FSH, ADH) and conducting the pituitary stimulation test. The severeness of all symptoms was slightly improved after substitution with antidiuretic hormone at 0.4 microgram/die and administration of hydrocortisone at 50 mg/die. Administration of amantadine sulphate at 0.6 g/die and L-dopa at 187.5 mg/die for 14 days resulted in a complete regression of the parkinsonism. After administration of aciclovir at 2.25 g/die for 21 days a complete regression of the clinical symptoms could be reached in connection with a decrease of 90% in number and size of cerebral contrasting foci in the magnetic resonance imaging of the head. Three month after therapy, clinical examination and blood serum analysis revealed persistent panhypopituitarism. The present case report is the first description of a viral infection on of the central nervous system (CNS) in combination with parkinsonism, diabetes insipidus, persistent panhypopituitarism and hyperprolactinemia. Early treatment of viral infections of the brain can improve a patient's prognosis dramatically. Early determination and early treatment of a patient's neurohumoral parameters is therefore critical to prevent or reverse early mental status changes like attention disturbances, alterations of personality and behavior, apathy, and slowed cognition.

A number of basically very different factors may affect the central nervous system and result in progressive loss of mental or physical functions immediately or after a latent period of decades, possibly due to the initial factor being combined with an additive effect of aging. Intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces degeneration of the basal ganglia. Various vira e.g. poliovirus and retrovirus may give rise to acute or late effects after several years. The Concentration Camp Syndrome may lead to a dementing illness with a latency of 10-30 years. Signs of progressive degenerative CNS disease should give rise to considerations of possible provoking factors earlier in the patient's life history.

The role of the hippocampus in retrograde amnesia remains controversial and poorly understood. Two cases are reported of discrete bilateral hippocampal damage, one of which was a rare case of limbic encephalitis secondary to the human herpes virus 6. Detailed memory testing showed marked anterograde memory impairment, but only mild, temporally-limited retrograde amnesia that covered a period of several years in both autobiographical and factual knowledge domains. The absence of extensive retrograde amnesia in these two cases points to a time-limited role for the hippocampus in the retrieval of retrograde memories, and suggests that entorhinal, perirhinal, parahippocampal, or neocortical areas of the temporal lobe may be more critical than the hippocampus proper for long-term retrograde memory functioning. Our findings offer general support to theories of memory consolidation that propose a gradual transfer of memory from hippocampal to neocortical dependency.

We report the naming performances of a 25 year-old woman with a left internal and inferior temporal lesion caused by herpes encephalitis who showed a preferential impairment for naming man-made objects. Evidence for category-specific effect was provided by a stepwise logistic regression using 171 pictures characterized by several parameters (words frequency, diversity of responses, length, name agreement, majoritary response, familiarity, visual complexity and canonicity). Analyses were realized over a 5 month period. Methodological considerations, anatomic correlations and arguments suggesting lexical access or semantic storage disturbance are discussed.

Patients with frontal, temporal lobe, or diencephalic lesions were compared with healthy controls on measures of recall and recognition memory for word lists. Exposure times were titrated to match recognition memory scores 30 s after the end of word-list presentation as closely as possible. Using this technique, we failed to find a disproportionate impairment in recall memory in either the frontal lobe lesion patients or in the amnesic (temporal lobe and diencephalic) patients, compared with healthy controls. Consistent with this finding, performance on these tasks showed highly significant correlations with anterograde memory quotients (despite the titration procedure), but not with executive/frontal function tasks. On the other hand, the frontal lobe lesion group showed disproportionate benefit in the recall of semantically categorised words, compared with unrelated words. This may indicate an impairment in retrieval or access, compared with the amnesic (temporal lobe and diencephalic) patients, and/or an inability to organise their learning of unrelated words spontaneously, compared with healthy controls.

This study aimed to characterize the qualitative pattern of focal retrograde memory impairment shown by a post-encephalitic patient (AV). AV's memory deficit encompassed autobiographical data, public events and famous people. In a public events questionnaire, she demonstrated a smooth negative temporal gradient with good recollection of events that occurred about 15 years before the disease but poor memory of more recent events. Her visual input lexicon was unimpaired, as demonstrated by normal lexicality judgment for words and normal familiarity judgment for proper names, but she was poor in familiarity judgment for famous faces (prosopagnosia) and in accessing the meaning of words or specific information about people. The cerebral MRI demonstrated widespread abnormal intensity areas encroaching upon the white matter of temporal, parietal and occipital lobes but sparing temporal poles and orbito-frontal cortex.

We tested amnesic and control subjects on a task which required the recognition of single, difficult to name colours, after delays ranging from 7 seconds to 120 seconds after performance of the two subject groups had been matched at the shortest delay by giving the amnesic patients longer study time. The amnesic patients showed abnormally fast forgetting over the two minute period. Furthermore, a subgroup of nine subjects with presumed damage to midline diencephalic structures (Korsakoff's syndrome) were found to forget as fast as a group of six subjects with presumed medial temporal lobe damage (herpes simplex encephalitis). These results contrast both with studies using the Huppert and Piercy procedure and those using the Brown-Peterson task, none of which have shown convincing evidence of accelerated forgetting in medial temporal lobe or diencephalic amnesia.

We report a double dissociation between visuo-spatial abilities and semantic knowledge (knowledge of the names and attributes of objects and people), in two brain-injured people with longstanding stable impairments, using a wide range of tests to explore the extent of the dissociation, MU, who has bilateral lesions of occipito-parietal cortex, shows severe spatial disorientation with relatively well-preserved semantic knowledge. He is contrasted with JBR, who has bilateral temporal lobe damage and shows severe semantic problems and no impairment on visuo-spatial tasks. Our findings thus demonstrate a double dissociation between the performance of semantic and spatial tasks by MU and JBR. This pattern is consistent with Ungerleider and Mishkin's (1982) neurophysiological hypothesis of separable cortical visual pathways; one which is specialised for spatial perception and follows a dorsal route from occipital to parietal lobes, and the other following a more ventral route from occipital to temporal lobes, whose target is semantic information needed in specifying what an object is.

We report the neuropsychological findings of two patients (LF and EA) with herpes simplex encephalitis. Both patients presented a greater deficit for living than non-living categories in a number of tasks, although EA was much more impaired than LF. We controlled the several stimulus variables that might affect the performance and could demonstrate that the dissociation was not artifactual. Neither LF nor EA revealed a selective or preferential involvement of perceptual semantic knowledge, and both showed a homogeneous impairment of perceptual and associative encyclopaedic notions. At a second examination, carried out from 1 to 2 years later, LF showed a good recovery, whereas EA's improvement was confined to the non-living categories. The lesion of both patients affected the left temporal pole and the basal neocortical regions of the left temporal lobe. The involvement of limbic areas was more marked in LF, while the Wernicke area and the posterior parts of the middle and inferior temporal gyri were only involved in EA. Besides the basal temporal areas, also the posterior temporal regions are likely to play a role in determining the clinical picture of such patients, and their prospect of recovery.

We report a patient with prominent autobiographical memory (ABM) impairment, and discussed possible mechanisms of her deficits. The patient was a 36-year-old woman who suffered from herpes simplex encephalitis in November 1994. Four months after the onset, the neuropsychological examination disclosed that her intelligence, attention, language and frontal lobe functions were normal. Moderate anterograde amnesia was evident for visual materials, and she showed difficulties in retrieving visual images. Deficits in verbal learning were minimal. In contrast, her retrograde amnesia (RA) was severe. Further analyses clarified that memory for public events and personal semantic memory were relatively well preserved whereas ABM was severely impaired with no evidence of temporal gradient. Her performance on the ABM questionnaire was even worse than that of alcoholic Korsakoff patients. Interestingly, however, deficits in memory for public events also emerged when questions were presented with pictures instead of ordinary verbal questionnaires. The results suggest that her principle deficits consisted in utilizing visual information of the past events. Her access to and manipulation of the past visual representation/images were impaired. Consequently, her deficits were almost exclusive to ABM because visual information is most crucial for ABM. This material specific ABM impairment demonstrated in the present patient could be differentiated from nonspecific retrograde amnesia observed in typical focal RA patients. MRI, SPECT and PET demonstrated that the present patient had lesions basically in the right hemisphere, specifically in the medical temporal area including the hippocampus.

Objective: Follow up of cognitive sequelae of acute encephalitis and estimation of the frequency of persisting dementia., Methods: 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., Results: 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., Conclusion: 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.

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.

Studies of retrograde amnesia are reviewed. First, the issues of temporal gradients of retrograde amnesia are discussed. Second, the question of the anatomical substrates of this syndrome are considered. Finally, some evidence for fractionation of different classes of memoranda within the retrograde time period are presented.

Objective: To compare the cognitive defects after acute acyclovir treated herpes simplex encephalitis with those after other types of acute encephalitis., Methods: Seventy seven consecutive patients between 1985 and 1995 and 29 normal controls were studied. Of the 77 patients without concomitant neurological conditions, 17 had herpes simplex, one virus encephalitis (HSVE group), 27 had some other identified aetiology (non-HSVE group), and in 33 patients the cause was unknown. Acyclovir treatment was started less than four days after the first mental symptoms in 12 of 17 patients with HSVE. A thorough neuropsychological assessment was carried out about one month after the onset., Results: The HSVE group had deficits in verbal memory, verbal-semantic functions, and visuoperceptual functions more often than the non-HSVE group. The risk for cognitive defects was twofold to four-fold in the patients with HSVE compared with the non-HSVE patients. Two (12%) of the patients with HSVE and 12 (44%) of the non-HSVE patients were cognitively intact. Six patients with HSVE (46%) and 17 (89%) non-HSVE patients later returned to work. The lesions on CT or MRI were bilateral only in one patient with HSVE. The defects in the three patients with adenovirus infection were severe and resembled the amnesia after HSVE. Cognitive impairment, not previously reported, was found in encephalitis after rotavirus infection and epidemic nephropathy., Conclusion: The recovery in the HSVE group was better than expected based on the medical literature. On the other hand there were surprisingly severe cognitive defects in encephalitis after other viruses. With early acyclovir treatment patients with the least severe HSVE were equivalent to those with non-HSV encephalitis with good outcome whereas those with the most severe non-HSV encephalitis were equivalent to those with HSVE with poor outcome.

Objectives: To evaluate how often global amnesia syndrome is encountered as a sequel of herpes simplex virus type 1 encephalitis (HSVE) and in other types of acute encephalitides, and to evaluate whether there are qualitative differences in amnesia caused by different encephalitides., Subjects: Forty-five consecutive patients with encephalitis (mean age, 40.8 years) studied prospectively within a 5-year period, 8 of whom had HSVE. There were 24 normal controls., Measures: Neuropsychological assessment and memory evaluation after the acute stage of encephalitis, as well as at follow-up after 27.7 +/- 18.6 months., Results: Three patients (6%), including 1 with HSVE, had persistent anterc grade and retrograde memory defects, typical features of global amnesia. Twelve patients had anterograde amnesia in the first assessment. No statistically significant differences in the memory measures were found between the HSVE (n = 4) and the non-HSVE (n = 8) groups. Some patients had predominantly semantic difficulty, some had a "frontal-type" memory disorder, and in some patients rapid forgetting was the prominent feature., Conclusions: The frequency of amnesia can reliably be evaluated only in consecutive series of patients. Previous literature, mainly case reports, may give the impression that global amnesia is a common consequence of encephalitis. Our findings do not support that view. Furthermore, there are clear differences in the quality of the memory impairment between cases of acute encephalitides. Our findings suggest that amnesia as a consequence of encephalitis, even HSVE, should not be considered a uniform phenomenon.

The author (born 1943) shows which phases of "integration into the society" he has undergone since his brain fevers in 1994 and 1958. This paper continues his former paper [1], in which are referred the special relations between the author and his son (born 1984). As previously in his own case, after his son entered school, hardness of hearing was detected which had been caused by a brain infection. The paper shows similarities and differences in the pattern of symptoms and their social acceptance.

We tested the hypothesis that partial forms of retrograde amnesia were associated with highly asymmetric lesions to the inferior and anterior-medial temporal lobe. Postencephalitic subjects EK and DR were both impaired on standardized retrograde memory tests, but showed strikingly different profiles in cognitive tasks of name stem completion, name:face matching, temporal ordering, forced choice recognition, and occupational judgments of famous names and faces from the past 3 decades. EK sustained left inferior and anterior-medial temporal lobe lesion with a small right temporal polar lesion, and showed near-complete loss of retrieval, knowledge, and familiarity associated with famous names but minimal deficiencies with famous faces. DR sustained right inferior and anterior-medial temporal lobe lesion and showed a milder retrograde loss limited to utilizing famous face prompts in name stem completion, name:face matching, occupational judgments, and forced choice recognition. These impairments were also different from the memory retrieval deficit, but intact recognition shown by a case of ruptured anterior communicating artery aneurysm with presumed basal forebrain damage. We hypothesize that EK's extensive loss of famous name knowledge was related to left inferior temporal lobe damage, particularly in the lateral and medial occipitotemporal gyri. This region in the left temporal lobe may serve as a critical processing area for retrograde memory that permits activation of established semantic, temporal, and visual (i.e., facial) associations biographically dependent on the category of proper names. On the basis of connectional anatomy patterns in the nonhuman primate, this region receives extensive hippocampal output and is interconnected with the temporal polar region and cortical association areas, which have been implicated in retrieval and storage aspects of retrograde memory. In the right hemisphere, the occipitotemporal gyri may serve an important role in famous face processing as part of a bilateral neural network.

Objective: To determine the associations between HIV encephalitis and other central nervous system (CNS) pathology, viral burden, cognitive impairment, zidovudine therapy and risk group in AIDS patients., Design: Planned autopsy study in AIDS patients evaluated prospectively for numerous clinical parameters., Setting: Regional academic centre for clinical care and pathology examination of patients with HIV infection., Patients: Edinburgh cohort of HIV-positive patients prospectively assessed for cognitive impairment, immunosuppression and clinical course. Unbiased series of consecutive autopsies in 27 homosexual men and 39 drug-using patients with AIDS., Interventions: Zidovudine therapy monitored in all patients., Main Outcome Measures: Determination of CNS viral burden and pathology including immunocytochemically confirmed HIV encephalitis in injecting drug users (IDU) versus homosexual AIDS patients with known CD4 counts and cognitive function., Results: HIV encephalitis was present in 59% of IDU and 15% of homosexuals: 88% of patients with encephalitis had displayed cognitive impairment. HIV encephalitis was strongly associated with a high viral load and HIV p24 immunopositivity. Opportunistic infections and lymphomas were more common in homosexuals (63%) than in IDU (31%) and were associated with the degree of immunosuppression before death. Within both groups, prolonged zidovudine treatment was associated with a lower incidence of HIV encephalitis., Conclusions: This study documents two separate CNS outcomes in AIDS patients in that HIV encephalitis occurs independently of opportunistic infections and lymphomas and shows different associations with risk group, immunosuppression and antiviral treatment before death.

Objectives: The preferential involvement of living categories in naming impairment is well recognised in Herpes Simplex Encephalitis (HSE). In this paper we describe naming, neuropsychological and neuroradiological findings with seven fresh HSE cases., Material & Methods: Patients were given a picture naming task that included 60 items belonging to 6 different categories (three living, i.e. fruits, vegetables and animals and three non-living, i.e. furniture, vehicles and tools). In the statistical analysis several possible sources of bias as the frequency of the target word, the familiarity with the objects to name, the image complexity and other parameters were taken into account., Results: Four out of seven patients were significantly more impaired with living things. We describe their general cognitive profile and discuss the anatomo-functional aspects of category dissociation., Conclusion: Language impairment, disproportionately severe for the naming of living exemplars, is frequently observed in HSE, is clinically relevant and should be specifically investigated.

A woman, LB, while in recovery from a viral encephalitis, exhibited a delusion for place, which led her to insist that she was at home, in spite of compelling evidence to the contrary. Later, she developed a Capgras syndrome, that is, another misidentification syndrome. The patient was given a detailed neuropsychological evaluation to shed light on the mechanisms underlying her delusional misbelief. Two main deficits were in evidence: (1) a severe visual-spatial impairment, giving the patient a distorted perception of her surroundings; and (2) frontal lobe dysfunction, which played a critical role in her impulsive responses and lack of self-awareness. The pathogenesis of delusion for place and persons if discussed in light of these observations.

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.

A fundamental question about memory and cognition concerns how information is acquired about categories and concepts as the result of encounters with specific instances. We describe a profoundly amnesic patient (E.P.) who cannot learn and remember specific instances--i.e., he has no detectable declarative memory. Yet after inspecting a series of 40 training stimuli, he was normal at classifying novel stimuli according to whether they did or did not belong to the same category as the training stimuli. In contrast, he was unable to recognize a single stimulus after it was presented 40 times in succession. These findings demonstrate that the ability to classify novel items, after experience with other items in the same category, is a separate and parallel memory function of the brain, independent of the limbic and diencephalic structures essential for remembering individual stimulus items (declarative memory). Category-level knowledge can be acquired implicitly by cumulating information from multiple training examples in the absence of detectable conscious memory for the examples themselves.

This study describes a patient (SE) with temporal lobe injury resulting from Herpes Simplex Encephalitis, who displayed a previously unreported impairment in which his knowledge of associative and functional attributes of animals was disproportionately impaired by comparison with his knowledge of their sensory attributes (including their visual properties and characteristic sounds). His knowledge of man-made objects was preserved. A striking aspect of the present case was that the patient remained able to name many animals from their pictures, despite making gross errors in generating associative information about these same animals. This suggests that a semantic representation incorporating stored sensory knowledge may be sufficient for naming (at least for biological categories) and associative information may be unnecessary. Semantic knowledge may normally incorporate more information than is necessary for identification. SE's errors were found to be confabulatory and reconstructive in nature and it is argued that this aspect of his performance challenges passive conceptions of semantic memory couched in terms of a catalogue of stored representations. It is proposed that the patient's disorder affects a dynamic, constructive, and inferential component of his knowledge base, and that this component is sensitive to semantic category.