Form Of Encephalitis Research Articles

Japanese Encephalitis Complicated with Obstructive Hydrocephalus

Japanese Encephalitis (JE), caused by Japanese encephalitis virus (JEV), a flavi-virus, is the most significant aetiology of arboviral encephalitis worldwide. It has resulted in epidemics of encephalitis in the Indian subcontinent. Here, we report a case of 36-year-old female who presented with a short history of fever and headache followed by altered sensorium. Funduscopic examination revealed Papilloedema. Pyogenic or viral meningoencephalitis along with complicated malaria were kept as initial differential diagnosis. Magnetic Resonance Imaging (MRI) of brain revealed involvement of posterior limb of internal capsule and bilateral thalami in the form of haemorrhagic encephalitis along with obstructive hydrocephalus. Cerebro Spinal Fluid (CSF) serology (IgM ELISA) showed JE as the causative agent. Despite extensive literature search, we could not find a case of JE reported with hydrocephalus as a complication. This case highlights the typical and atypical features of JE including imaging findings and exemplifies the way, how diversely JE can present and would thus help in preparing management paradigms accordingly.

Anti- NMDA Receptor Antibody Encephalitis: - A Review of Nine Patients with Clinical Presentation, Investigations, Treatment and Outcome in Singapore

Objective: To report on epidemiology, clinical and laboratory features of patients diagnosed with anti-N-methyl-Daspartate receptor (NMDAR) encephalitis admitted to Singapore general hospital over the period of four years. This is the first study for the local population. Introduction: Anti –NMDA receptor encephalitis is a severe form of encephalitis that associates with antibodies against NMDA receptors resulting in a neuropsychiatric syndrome. It has been considered as a Paraneoplastic syndrome. Methods: Nine patients (6 female and 3 male) admitted to neurology unit from March 2010 to Oct 2013 were studied retrospectively. Diagnosis of anti-NMDA receptor antibody encephalitis was based on encephalitis plus positive CSF serology. Result: Younger age group affected more (range 16 to 65 years). Clinical presentation usually involves the triad of psychotic (100%); seizures (66%) and movement disorder (45%). Autonomic instability observed in two third (66%) of patients. Serum serology is positive only in 55% patients. CSF analysis was variable. MRI brain was largely unremarkable (77%). Tumour occurrence was seen in 66%; 83% in females, 33% in males. The outcome was favourable in two third patients with the best prognosis in female patients when the tumour was found and resected and worst in male patients with tumour unresected. Conclusion: Results are consistent with the current literature in terms of epidemiology, investigations and outcome. However, it requires the larger number of patients with longer follow-up to prove its association with a tumour in patients who has no evidence of malignancy at diagnosis.

Chapter 12 - Anti-NMDAR encephalitis and other glutamate and GABA receptor antibody encephalopathies

Over the last few year, antibodies to various central nervous system receptors, particularly the glutamate and γ-aminobutyric acid (GABA) receptors, have been found to be associated with autoimmune neurologic disorders. The receptors include the N-methyl-d-aspartate receptor (NMDAR), the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), the metabotropic glutamate receptors (mGluRs), and GABA type A and B receptors (respectively GABAAR and GABABR). Compared to the previously described paraneoplastic antibodies directed at intracellular targets, the patients with receptor antibodies are often younger, they less frequently have malignancies, and they respond better to immunotherapy. Many of the patients have limbic encephalitis with amnesia, disorientation, seizures, and psychological or psychiatric symptoms, but those with NMDAR antibodies usually develop a more widespread form of encephalitis, often leading to a decrease in consciousness and requirement for long-term intensive care treatment. The autoantibodies bind directly to the synaptic or extrasynaptic receptors on the membrane surface, and have direct effects on signal transduction in central synapses. These conditions are very important to recognize as the symptoms and complications can be fatal when not treated in time, whereas with immunotherapy many patients recover considerably.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A New Challenging Entity for Consultation-Liaison Psychiatrist

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a relatively newly identified autoimmune neuropsychiatric disorder that predominantly affects children and young adults. Although psychiatric symptoms are highly prevalent and frequently severe, it has mainly been reported in neurological, but not psychiatric, literature. Understanding this form of encephalitis, its quick diagnosis and which treatment to provide are of utmost importance for consultation-liaison (C-L) psychiatrists. The aim of this paper was to describe a case of anti-NMDAR encephalitis with severe psychiatric manifestations, who showed impressive recovery but required intensive involvement of the C-L psychiatry team. We emphasise the behavioural aspects, psychiatric symptoms and challenges faced by the CL consultant across the different phases of the treatment. We report the different treatment phases for a young woman with anti-NMDAR encephalitis who developed severe neuropsychiatric symptoms, with a focus on the role and challenges faced by the C-L psychiatrist. The literature is reviewed for each of these challenges. This case illustrated that even extremely severely affected patients may show impressive recovery, but require long lasting psychiatric care. C-L psychiatrists are faced with numerous challenges where only little literature is available. C-L psychiatrists play a pivotal role throughout the multidisciplinary care of patients with anti-NMDAR encephalitis and should be informed about this entity.

The Diagnosis and Treatment of Autoimmune Encephalitis.

Autoimmune encephalitis causes subacute deficits of memory and cognition, often followed by suppressed level of consciousness or coma. A careful history and examination may show early clues to particular autoimmune causes, such as neuromyotonia, hyperekplexia, psychosis, dystonia, or the presence of particular tumors. Ancillary testing with MRI and EEG may be helpful for excluding other causes, managing seizures, and, rarely, for identifying characteristic findings. Appropriate autoantibody testing can confirm specific diagnoses, although this is often done in parallel with exclusion of infectious and other causes. Autoimmune encephalitis may be divided into several groups of diseases: those with pathogenic antibodies to cell surface proteins, those with antibodies to intracellular synaptic proteins, T-cell diseases associated with antibodies to intracellular antigens, and those associated with other autoimmune disorders. Many forms of autoimmune encephalitis are paraneoplastic, and each of these conveys a distinct risk profile for various tumors. Tumor screening and, if necessary, treatment is essential to proper management. Most forms of autoimmune encephalitis respond to immune therapies, although powerful immune suppression for weeks or months may be needed in difficult cases. Autoimmune encephalitis may relapse, so follow-up care is important.

Antibody-Mediated Autoimmune Encephalopathies and Immunotherapies.

Over the last 15 years it has become clear that rare but highly recognizable diseases of the central nervous system (CNS), including newly identified forms of limbic encephalitis and other encephalopathies, are likely to be mediated by antibodies (Abs) to CNS proteins. The Abs are directed against membrane receptors and ion channel-associated proteins that are expressed on the surface of neurons in the CNS, such as N-methyl D-aspartate receptors and leucine-rich, glioma inactivated 1 protein and contactin-associated protein like 2, that are associated with voltage-gated potassium channels. The diseases are not invariably cancer-related and are therefore different from the classical paraneoplastic neurological diseases that are associated with, but not caused by, Abs to intracellular proteins. Most importantly, the new antibody-associated diseases almost invariably respond to immunotherapies with considerable and sometimes complete recovery, and there is convincing evidence of their pathogenicity in the relatively limited studies performed so far. Treatments include first-line steroids, intravenous immunoglobulins, and plasma exchange, and second-line rituximab and cyclophosphamide, followed in many cases by steroid-sparing agents in the long-term. This review focuses mainly on N-methyl D-aspartate receptor- and voltage-gated potassium channel complex-related Abs in adults, the clinical phenotypes, and treatment responses. Pediatric cases are referred to but not reviewed in detail. As there have been very few prospective studies, the conclusions regarding immunotherapies are based on retrospective studies.Electronic supplementary materialThe online version of this article (doi:10.1007/s13311-015-0410-6) contains supplementary material, which is available to authorized users.

Induced systemic listeriosis in Alectoris chukar chicks: clinical, histopathological and microbiological findings

1. Systemic listeriosis was induced in 14-d-old Chukar partridge chicks, Alectoris chukar, by intravenous injection of a suspension containing 106 cfu/ml of viable Listeria monocytogenes organisms to study the course of infection.2. Septicaemic and encephalitic forms of listeriosis were observed in all birds. Infection resulted in a fever response 8-h post-inoculation. Disease rapidly developed over a 24-h period with decreased activity, lethargy, ruffled feathers, huddling, listlessness, inability to stand, wing droop, decreased feed and water consumption, growth depression, neural disturbances and finally death. Gross and histopathological changes were observed in the myocardium, proventriculus, gizzard, intestine, pancreas, kidney, liver, spleen, lung, meninges and joints.3. The diversity of these clinical signs and lesions suggests a high susceptibility of Chukar partridge chicks to systemic listeriosis.

Autoimmune encephalitis following haematopoietic stem cell transplant: a new clinical entity or a previously unrecognised one?

Central nervous system (CNS) autoimmunity, characterized by the presence of antibodies binding to brain receptors, ion channels, and related proteins (1) is increasingly recognized in children (2). Childhood-onset autoimmune encephalitis may be associated with tumours, particularly in post-pubertal girls with N-Methyl-D-aspartate receptor (NMDAR) antibody encephalitis (3), but the majority of these encephalitides are presumed to have a post infectious trigger (1,4). Recently, in a large single-centre study of 164 Australian children presenting with encephalitis, 10% were identified as having an autoimmune aetiology, a frequency which surpassed that of any single virus identified (5), mirroring cases reported in the California encephalitis project, where the frequency of NMDAR antibody encephalitis surpassed that of any of the identified viral encephalitides (6). This discovery, that several forms of encephalitis result from neuronal antibodies, and are immunotherapy-responsive, has led to a paradigm shift in the diagnostic approach with a focus on how to recognize, diagnose and treat these conditions early (2).

Cerebral Toxoplasmosis in HIV/ Aids Patient- A Case Report

Toxoplasmosis is caused by T. gondii infection in patients with AIDS accounting for 50 – 70% of all mass lesion in this population & is an important cause of focal lesion in this group. As HIV infection is becoming more prevalent, CNS complications of HIV are being encountered more and more in routine clinical practice. Toxoplasmosis associated with HIV infection is mainly caused by reactivation of a chronic infection and manifests as toxoplasmic encephalitis. Typically, toxoplasmic encephalitis has a subacute onset with focal neurological abnormalities characteristically accompanied by headache, altered mental status and fever. Rarely it can present as a rapidly fatal form of diffuse encephalitis. Extracerebral toxoplasmosis can also occur. The most commonly used serological tests detect the presence of anti T. gondii IgG and IgM antibodies. Neuroimaging modalities especially computed tomography (CT) and Magnetic resonance imaging (MRI) are also indispensable. The patient was started on Tab. Pyrimethamine 100mg daily and Sulphadiazine 1gm 6 hourly for 4 weeks with marked improvement at the end of 4 weeks.Bangladesh J Medicine Jul 2014; 25 (2) : 76-77

Cerebrospinal Fluid Biomarkers of Japanese Encephalitis

Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia. Acute encephalitis syndrome (AES) is a group of central nervous system (CNS) disorders caused by a wide range of viruses, bacteria, fungi, chemicals and toxins. It is important to distinguish between various forms of infectious encephalitis with similar clinical manifestations in order to ensure specific and accurate diagnosis and development of subsequent therapeutic strategies. Cerebrospinal fluid (CSF) is in direct contact with the CNS and hence it is considered to be an excellent source for identifying biomarkers for various neurological disorders. With the recent advancement in proteomic methodologies, the field of biomarker research has received a remarkable boost. The present study identifies potential biomarkers for JE using a proteomics based approach. The CSF proteomes from ten patients each with JE and Non-JE acute encephalitis were analyzed by 2D gel electrophoresis followed by mass spectrometry. Vitamin D-binding protein (DBP), fibrinogen gamma chain, fibrinogen beta chain, complement C4-B, complement C3 and cytoplasmic actin were found to be significantly elevated in case of JE indicating severe disruption of the blood brain barrier and DBP can be suggested to be an important diagnostic marker.

Guillain-Barré syndrome after varicella-zoster virus infection

Guillain-Barre syndrome (GBS) is an acute inflammatory, demyelinating polyradiculoneuropathy. The neurological complications of varicella-zoster virus (VZV) infection are usually cerebellar ataxia and other forms of encephalitis. VZV is associated with only 1% of the GBS cases. GBS may present as a clinical picture mimicking encephalitis. We report a patient with GBS who presented with altered consciousness and flaccid paralysis of the legs, three weeks after VZV infection.

Cerebrospinal Fluid Biomarkers of Japanese Encephalitis

Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia. Acute encephalitis syndrome (AES) is a group of central nervous system (CNS) disorders caused by a wide range of viruses, bacteria, fungi, chemicals and toxins. It is important to distinguish between various forms of infectious encephalitis with similar clinical manifestations in order to ensure specific and accurate diagnosis and development of subsequent therapeutic strategies. Cerebrospinal fluid (CSF) is in direct contact with the CNS and hence it is considered to be an excellent source for identifying biomarkers for various neurological disorders. With the recent advancement in proteomic methodologies, the field of biomarker research has received a remarkable boost. The present study identifies potential biomarkers for JE using a proteomics based approach. The CSF proteomes from ten patients each with JE and Non-JE acute encephalitis were analyzed by 2D gel electrophoresis followed by mass spectrometry. Vitamin D-binding protein (DBP), fibrinogen gamma chain, fibrinogen beta chain, complement C4-B, complement C3 and cytoplasmic actin were found to be significantly elevated in case of JE indicating severe disruption of the blood brain barrier and DBP can be suggested to be an important diagnostic marker.

Sandfly fever virus as a cause of encephalitis in Egypt

Sandfly fever (SF) viruses are known to spread in the Mideteranean basin and some species were shown to cause different forms of encephalitis. This case report describes an 8-year-old girl who was admitted to a rural hospital in Egypt with fever and myalgia. The clinical presentation included signs suggesting cerebrospinal infection. Cerebrospinal fluid aspects suggested viral infection. Virological diagnosis was obtained by serological tests, and reverse transcriptase-polymerase chain reaction and virus isolation cultures against a panel of viruses. Enzyme-linked immunosorbent assay IgM antibodies and plaque reduction neutralization tests suggested that sandfly Scilian virus is the causing etiology.

The emergence of enterovirus 71 as a major cause of acute neurological disease in young children of the Asia-Pacific region

Since its discovery in 1970, enterovirus 71 (EV71) has increasingly been recognized as a cause of epidemics of hand-foot-and-mouth disease (HFMD) associated with severe neurological complications in a proportion of cases. There has been a large increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997. Recent HFMD epidemics have been associated with a severe form of brainstem encephalitis associated with pulmonary edema and high case-fatality rates. The emergence of EV71 activity in the Asia-Pacific region has been associated with the circulation of several distinct genetic lineages that appear to be undergoing rapid evolutionary change. In this review, I will present a synopsis of recent research into the epidemiology and evolution of EV71 in the Asia-Pacific region, the neurological diseases attributable to EV71 infection and the prospects for control of EV71 infections through public health interventions and the development of new antiviral agents and vaccines.

Cerebrospinal Fluid Biomarkers of Japanese Encephalitis.

Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia. Acute encephalitis syndrome (AES) is a group of central nervous system (CNS) disorders caused by a wide range of viruses, bacteria, fungi, chemicals and toxins. It is important to distinguish between various forms of infectious encephalitis with similar clinical manifestations in order to ensure specific and accurate diagnosis and development of subsequent therapeutic strategies. Cerebrospinal fluid (CSF) is in direct contact with the CNS and hence it is considered to be an excellent source for identifying biomarkers for various neurological disorders. With the recent advancement in proteomic methodologies, the field of biomarker research has received a remarkable boost. The present study identifies potential biomarkers for JE using a proteomics based approach. The CSF proteomes from ten patients each with JE and Non-JE acute encephalitis were analyzed by 2D gel electrophoresis followed by mass spectrometry. Vitamin D-binding protein (DBP), fibrinogen gamma chain, fibrinogen beta chain, complement C4-B, complement C3 and cytoplasmic actin were found to be significantly elevated in case of JE indicating severe disruption of the blood brain barrier and DBP can be suggested to be an important diagnostic marker.

Paediatric Acute Encephalitis: Infection and Inflammation

Encephalitis is a multifaceted syndrome with a myriad of clinical presentations. It is defined as inflammation of the brain with functional disturbance. Infectious diseases, particularly viruses, and autoimmune disorders are the commonest causes in children. Young infants have the highest burden of disease for most infectious causes. Recent advances include the publication of international consensus guidelines, emergence of new aetiologies including human parechoviruses and better characterisation of known infectious causes, including enterovirus 71, which continue to cause large epidemics, death and impairment in children although a number promising vaccines are on the horizon; and neurological syndromes associated with influenza which occur most commonly in children who are not immunised against the virus. Understanding of childhood autoimmune encephalopathies is also rapidly expanding including responses to immunomodulation and prognosis. Future research should see better understanding of the pathogenesis of all forms of encephalitis, with hope for advances in therapy and prevention.

Paving the Way to Understand Autoantibody-Mediated Epilepsy on the Molecular Level.

Correct function of neuronal networks is enabled by a delicate interplay among neurons communicating with each other. One of the keys is the communication at chemical synapses where neurotransmitters like glutamate, GABA, and glycine enable signal transfer over the synaptic cleft. Thereby, the neurotransmitters are released from the presynapse and bind as ligands to specific receptors at the postsynaptic side to allow for modulation of the postsynaptic membrane potentials. The postsynaptic electrical signal, which is highly modulated by voltage-gated ion channels, spreads over the dendritic tree and is thus integrated to allow for generation of action potentials at the axon hillock. This concert of receptors and voltage-gated ion channels depends on correct function of all its components. Misfunction of receptors and/or voltage-gated potassium channels (VGKC) leads to diverse adverse effects in patients. Such malfunctions can be the result of inherited genetic alterations or pharmacological side effects by drugs. Recently, autoantibodies targeting receptor or channel complexes like NMDAR, AMPAR, GABA-receptors, glycine receptors, LGI1 or CASPR2 (previously termed as VGKC-complex antibodies) have been discovered. The presence of specific autoantibodies against these targets associates with severe forms of antibody-mediated encephalitis. Understanding the molecular details of autoantibody actions on receptor and VGKC complexes is highly desirable and may open the path to develop specific therapies to treat humoral autoimmune encephalitis. Here, we summarize the current knowledge and discuss technical approaches to fill the gap of knowledge. These techniques include electrophysiology, biochemical approaches for epitope mapping, and in silico modeling to simulate molecular interactions between autoantibody and its molecular target.

Clinical Features of Infectious and Autoantibody Encephalitis.

Investigators from University of Sydney, Australia; John Radcliffe Hospital, Oxford, UK; Imperial College, London, UK; and other centers, studied infectious, immune-mediated/autoantibody associated and unknown forms of encephalitis, including frequencies, clinical and radiological phenotypes, and long-term outcome.

CSF findings in patients with anti-N-methyl-d-aspartate receptor-encephalitis

PurposeAnti-NMDAR-encephalitis is a recently described form of autoimmune encephalitis. Here, we characterize CSF changes in Chinese patients with anti-NMDAR encephalitis, and explore the relationship between CSF findings and disease outcome. MethodsThe presence of NMDAR antibodies in serum or CSF samples was evaluated in patients diagnosed with encephalitis between October 1, 2010 and August 1, 2014 at the West China Hospital. All patients fulfilling our diagnostic criteria were included and CSF findings were analyzed. Patient outcome was assessed after 4, 8, 12, 16, 20, and 24 months using the modified Rankin scale (mRS). ResultsOut of 3000 people with encephalitis screened, 43 patients were anti-NMDAR antibody positive in CSF or serum and included in this study. 62.8% of the patients identified with positive CSFs had positive serum anti-NMDAR samples, while 100% patients with positive serum had positive CSF samples. In the CSF white cell counts were elevated in 58.1% of cases; protein was increased in 18.6%; QAlb>Qlim(Alb) of the blood–CSF barrier was found in 29.3%; intrathecal immunoglobulin synthesis was detected in 17.1%, and 39.5% patients exhibited increased CSF pressures. A longer follow-up period was associated with better outcomes. There was no relationship between changes in CSF findings and outcome. ConclusionThe sensitivity of NMDA receptor antibody testing is higher in CSF compared to serum. Other CSF abnormalities are present in some patients with Anti-NMDAR-encephalitis, however these changes do not appear to affect prognosis.

Infectious and autoantibody-associated encephalitis: clinical features and long-term outcome.

Pediatric encephalitis has a wide range of etiologies, clinical presentations, and outcomes. This study seeks to classify and characterize infectious, immune-mediated/autoantibody-associated and unknown forms of encephalitis, including relative frequencies, clinical and radiologic phenotypes, and long-term outcome. By using consensus definitions and a retrospective single-center cohort of 164 Australian children, we performed clinical and radiologic phenotyping blinded to etiology and outcomes, and we tested archived acute sera for autoantibodies to N-methyl-D-aspartate receptor, voltage-gated potassium channel complex, and other neuronal antigens. Through telephone interviews, we defined outcomes by using the Liverpool Outcome Score (for encephalitis). An infectious encephalitis occurred in 30%, infection-associated encephalopathy in 8%, immune-mediated/autoantibody-associated encephalitis in 34%, and unknown encephalitis in 28%. In descending order of frequency, the larger subgroups were acute disseminated encephalomyelitis (21%), enterovirus (12%), Mycoplasma pneumoniae (7%), N-methyl-D-aspartate receptor antibody (6%), herpes simplex virus (5%), and voltage-gated potassium channel complex antibody (4%). Movement disorders, psychiatric symptoms, agitation, speech dysfunction, cerebrospinal fluid oligoclonal bands, MRI limbic encephalitis, and clinical relapse were more common in patients with autoantibodies. An abnormal outcome occurred in 49% of patients after a median follow-up of 5.8 years. Herpes simplex virus and unknown forms had the worst outcomes. According to our multivariate analysis, an abnormal outcome was more common in patients with status epilepticus, magnetic resonance diffusion restriction, and ICU admission. We have defined clinical and radiologic phenotypes of infectious and immune-mediated/autoantibody-associated encephalitis. In this resource-rich cohort, immune-mediated/autoantibody-associated etiologies are common, and the recognition and treatment of these entities should be a clinical priority.