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Journal of Neurology, Neurosurgery, and... Jul 2021The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking.... (Review)
Review
The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. Corticosteroids alone or combined with other agents (intravenous IG or plasmapheresis) were selected as a first-line therapy by 84% of responders for patients with a general presentation, 74% for patients presenting with faciobrachial dystonic seizures, 63% for NMDAR-IgG encephalitis and 48.5% for classical paraneoplastic encephalitis. Half the responders indicated they would add a second-line agent only if there was no response to more than one first-line agent, 32% indicated adding a second-line agent if there was no response to one first-line agent, while only 15% indicated using a second-line agent in all patients. As for the preferred second-line agent, 80% of responders chose rituximab while only 10% chose cyclophosphamide in a clinical scenario with unknown antibodies. Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.
Topics: Adrenal Cortex Hormones; Autoimmune Diseases; Encephalitis; Humans; Immunoglobulins, Intravenous; Plasmapheresis; Treatment Outcome
PubMed: 33649022
DOI: 10.1136/jnnp-2020-325300 -
Practical Neurology Oct 2021Autoimmune encephalitis defines brain inflammation caused by a misdirected immune response against self-antigens expressed in the central nervous system. It comprises a... (Review)
Review
Autoimmune encephalitis defines brain inflammation caused by a misdirected immune response against self-antigens expressed in the central nervous system. It comprises a heterogeneous group of disorders that are at least as common as infectious causes of encephalitis. The rapid and ongoing expansion of this field has been driven by the identification of several pathogenic autoantibodies that cause polysymptomatic neurological and neuropsychiatric diseases. These conditions often show highly distinctive cognitive, seizure and movement disorder phenotypes, making them clinically recognisable. Their early identification and treatment improve patient outcomes, and may aid rapid diagnosis of an underlying associated tumour. Here we summarise the well-known autoantibody-mediated encephalitis syndromes with neuronal cell-surface antigens. We focus on practical aspects of their diagnosis and treatment, offer our clinical experiences of managing such cases and highlight more basic neuroimmunological advances that will inform their future diagnosis and treatments.
Topics: Autoantibodies; Encephalitis; Hashimoto Disease; Humans; Movement Disorders
PubMed: 34108243
DOI: 10.1136/practneurol-2020-002567 -
Clinical Medicine (London, England) Mar 2018Encephalitis, inflammation of the brain, is most commonly caused by a viral infection (especially herpes simplex virus [HSV] type 1 in the UK) although autoimmune... (Review)
Review
Encephalitis, inflammation of the brain, is most commonly caused by a viral infection (especially herpes simplex virus [HSV] type 1 in the UK) although autoimmune causes, such as N-methyl D-aspartate receptor (NMDAR) antibody encephalitis, are increasingly recognised. Most patients present with a change in consciousness level and may have fever, seizures, movement disorder or focal neurological deficits. Diagnosis hinges crucially on lumbar puncture and cerebrospinal fluid (CSF) examination, but imaging and electroencephalography (EEG) may also be helpful. Treatment of HSV encephalitis with aciclovir dramatically improves outcome, but the optimal management of autoimmune encephalitis is still uncertain. Many patients with encephalitis are left with residual physical or neuropsychological deficits which require long-term multidisciplinary management. Here we review assessment of patients with suspected encephalitis, general aspects of management and areas of ongoing research.
Topics: Acute Disease; Biomedical Research; Brain; Encephalitis; Humans
PubMed: 29626021
DOI: 10.7861/clinmedicine.18-2-155 -
Current Neurology and Neuroscience... Apr 2023To describe the clinical manifestations of Hashimoto's encephalopathy (HE) and discuss its pathogenesis in light of recent research. (Review)
Review
PURPOSE OF REVIEW
To describe the clinical manifestations of Hashimoto's encephalopathy (HE) and discuss its pathogenesis in light of recent research.
RECENT FINDINGS
The pathogenesis of HE is uncertain. Available evidences point towards an autoimmune etiology due to vasculitis or other inflammatory process. Detection of thyroid antibodies - antithyroid peroxidase and anti-thyroglobulin are essential for diagnosis. Autoimmune encephalitis including Anti-IgLON5 disease needs to be excluded in suspected cases with appropriate tests for neuronal surface antibodies. Detection of thyroid autoantibodies is nonspecific, as these can be detected in some normal individuals and in other autoimmune diseases. In recent years, attention has turned to an aggressive form of Hashimoto's thyroiditis accompanied by elevated serum IgG4 levels in younger males with very high levels of thyroid antibodies. The role of the thyroid autoantibodies in the central nervous system (CNS) tissue damage remains unclear and these can act only as markers for diagnosis. Conversely, they have a role to play in determining the thyroid pathology - more glandular fibrosis associated with thyro-peroxidase antibody than with the thyroglobulin antibody. HE is a syndrome characterized by altered mental status, confusion, hallucinations, delusions, and sometimes seizures, in association with high serum anti-thyroid antibody concentration that is usually responsive to glucocorticoid therapy. Diagnosis requires the exclusion of other causes of encephalopathies and encephalitis including autoimmune encephalitis associated with neuronal surface antibodies and paraneoplastic ones. Diagnosis also is dependent on the demonstration of thyroid autoantibodies in serum. Since there is no direct pathophysiologic link between antithyroid antibodies, Hashimoto thyroiditis and the cerebral syndrome, the nomenclature HE could be misleading. The response to steroids led to a renaming of the syndrome to steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT), though some cases do not respond to steroids. In recent years, attention has turned to an aggressive form of Hashimoto's thyroiditis accompanied by elevated serum IgG4 levels (IgG4-related disease). This is characterized by a higher incidence in men (5:1) than in women, onset at a younger age, more intense thyroid inflammation and higher antithyroid antibody titters. Such patients have excessive production of IgG4 + plasmacytes, which infiltrate various organs leading to their fibrosis and sclerosis, sometimes resulting in inflammatory tumors. HE is treated with corticosteroids along with treatment of the dysthyroid condition, if any. There are yet no guidelines regarding steroid dose and/or duration.
Topics: Male; Humans; Female; Hashimoto Disease; Encephalitis; Brain Diseases; Autoantibodies; Steroids; Immunoglobulin G; Fibrosis; Autoimmune Diseases of the Nervous System
PubMed: 36853554
DOI: 10.1007/s11910-023-01255-5 -
Infectious Disease Clinics of North... Mar 2018Encephalitis is an uncommon but severe disease characterized by neurologic dysfunction with central nervous system inflammation. Children with encephalitis should... (Review)
Review
Encephalitis is an uncommon but severe disease characterized by neurologic dysfunction with central nervous system inflammation. Children with encephalitis should receive supportive care and empiric therapies for common and treatable causes while prioritizing diagnostic evaluation for common, treatable, and high-risk conditions. Even with an extensive diagnostic workup, an infectious cause is identified in less than half of cases, suggesting a role for postinfectious or noninfectious processes.
Topics: Arboviruses; Brain; Child; Diagnosis, Differential; Encephalitis; Enterovirus; Female; Herpes Simplex; Humans; Male; Meningoencephalitis; Myelitis; United States
PubMed: 29224854
DOI: 10.1016/j.idc.2017.10.007 -
The Lancet. Neurology Feb 2014Rasmussen's encephalitis is a rare chronic neurological disorder, characterised by unilateral inflammation of the cerebral cortex, drug-resistant epilepsy, and... (Review)
Review
Rasmussen's encephalitis is a rare chronic neurological disorder, characterised by unilateral inflammation of the cerebral cortex, drug-resistant epilepsy, and progressive neurological and cognitive deterioration. Neuropathological and immunological studies support the notion that Rasmussen's encephalitis is probably driven by a T-cell response to one or more antigenic epitopes, with potential additional contribution by autoantibodies. Careful analysis of the association between histopathology and clinical presentation suggests that initial damage to the brain is mediated by T cells and microglia, suggesting a window for treatment if Rasmussen's encephalitis can be diagnosed early. Advances in neuroimaging suggest that progression of the inflammatory process seen with MRI might be a good biomarker in Rasmussen's encephalitis. For many patients, families, and doctors, choosing the right time to move from medical management to surgery is a real therapeutic dilemma. Cerebral hemispherectomy remains the only cure for seizures, but there are inevitable functional compromises. Decisions of whether or when surgery should be undertaken are challenging in the absence of a dense neurological deficit, and vary by institutional experience. Further, the optimum time for surgery, to give the best language and cognitive outcome, is not yet well understood. Immunomodulatory treatments seem to slow rather than halt disease progression in Rasmussen's encephalitis, without changing the eventual outcome.
Topics: Encephalitis; Humans
PubMed: 24457189
DOI: 10.1016/S1474-4422(13)70260-6 -
F1000Research 2020Encephalitis is an important cause of morbidity, mortality, and permanent neurologic sequelae globally. Causes are diverse and include viral and non-viral infections... (Review)
Review
Encephalitis is an important cause of morbidity, mortality, and permanent neurologic sequelae globally. Causes are diverse and include viral and non-viral infections of the brain as well as autoimmune processes. In the West, the autoimmune encephalitides are now more common than any single infectious cause, but, in Asia, infectious causes are still more common. In 2006, the World Health Organization coined the term "acute encephalitis syndrome", which simply means acute onset of fever with convulsions or altered consciousness or both. In 2013, the International Encephalitis Consortium set criteria for diagnosis of encephalitis on basis of clinical and laboratory features. The most important infectious cause in the West is herpes simplex virus, but globally Japanese encephalitis (JE) remains the single largest cause. Etiologic diagnosis is difficult because of the large number of agents that can cause encephalitis. Also, the responsible virus may be detectable only in the brain and is either absent or transiently found in blood or cerebrospinal fluid (CSF). Virological diagnosis is complex, expensive, and time-consuming. Different centres could make their own algorithms for investigation in accordance with the local etiologic scenarios. Magnetic resonance imaging (MRI) and electroencephalography are specific for few agents. Clinically, severity may vary widely. A severe case may manifest with fever, convulsions, coma, neurologic deficits, and death. Autoimmune encephalitis (AIE) includes two major categories: (i) classic paraneoplastic limbic encephalitis (LE) with autoantibodies against intracellular neuronal antigens (Eg: Hu and Ma2) and (ii) new-type AIE with autoantibodies to neuronal surface or synaptic antigens (Eg: anti-N-methyl-D-aspartate receptor). AIE has prominent psychiatric manifestations: psychosis, aggression, mutism, memory loss, euphoria, or fear. Seizures, cognitive decline, coma, and abnormal movements are common. Symptoms may fluctuate rapidly. Treatment is largely supportive. Specific treatment is available for herpesvirus group and non-viral infections. Various forms of immunotherapy are used for AIE.
Topics: Acute Disease; Animals; Autoantibodies; Encephalitis; Hashimoto Disease; Humans; Receptors, N-Methyl-D-Aspartate
PubMed: 32047620
DOI: 10.12688/f1000research.20634.1 -
Der Nervenarzt Jun 2023Detection of autoantibodies against neurons and glia cells has brought about the early and specific diagnosis of autoimmune encephalitis in patients with variable... (Review)
Review
Detection of autoantibodies against neurons and glia cells has brought about the early and specific diagnosis of autoimmune encephalitis in patients with variable neurological and psychiatric symptoms. Growing knowledge not only resulted in profound changes in treatment algorithms including immunotherapy but also in the understanding of disease mechanisms and etiological factors. The still increasing numbers of new autoantibodies calls for continuous updates on the state of the art in antibody diagnostics, frequencies of associated tumors and the clinical spectrum linked to each antibody, which can range from mood changes, cognitive impairment and epileptic seizures to abnormal movements, autonomic dysfunction and impaired levels of consciousness. This article summarizes the recent developments in the predominant clinical presentations of autoimmune encephalitis patients in imaging and cerebrospinal fluid diagnostics and also in prognostic markers, in the establishment of innovative immunotherapies, in the use of diagnostic pathways even before the results of the antibody tests are available and the understanding of the autoimmune etiology.
Topics: Humans; Encephalitis; Autoantibodies; Hashimoto Disease; Autoimmune Diseases of the Nervous System
PubMed: 36515716
DOI: 10.1007/s00115-022-01411-1 -
The New England Journal of Medicine Mar 2018
Review
Topics: Adult; Antigens, Surface; Autoantibodies; Autoimmune Diseases of the Nervous System; Child; Encephalitis; Female; Genetic Predisposition to Disease; Humans; Magnetic Resonance Imaging; Male; Neurons
PubMed: 29490181
DOI: 10.1056/NEJMra1708712 -
The Lancet. Neurology Jan 2011Since its discovery in 2007, the encephalitis associated with antibodies against the N-methyl-D-aspartate receptor (NMDAR) has entered the mainstream of neurology and... (Review)
Review
Since its discovery in 2007, the encephalitis associated with antibodies against the N-methyl-D-aspartate receptor (NMDAR) has entered the mainstream of neurology and other disciplines. Most patients with anti-NMDAR encephalitis develop a multistage illness that progresses from psychosis, memory deficits, seizures, and language disintegration into a state of unresponsiveness with catatonic features often associated with abnormal movements, and autonomic and breathing instability. The disorder predominantly affects children and young adults, occurs with or without tumour association, and responds to treatment but can relapse. The presence of a tumour (usually an ovarian teratoma) is dependent on age, sex, and ethnicity, being more frequent in women older than 18 years, and slightly more predominant in black women than it is in white women. Patients treated with tumour resection and immunotherapy (corticosteroids, intravenous immunoglobulin, or plasma exchange) respond faster to treatment and less frequently need second-line immunotherapy (cyclophosphamide or rituximab, or both) than do patients without a tumour who receive similar initial immunotherapy. More than 75% of all patients have substantial recovery that occurs in inverse order of symptom development and is associated with a decline of antibody titres. Patients' antibodies cause a titre-dependent, reversible decrease of synaptic NMDAR by a mechanism of crosslinking and internalisation. On the basis of models of pharmacological or genetic disruption of NMDAR, these antibody effects reveal a probable pathogenic relation between the depletion of receptors and the clinical features of anti-NMDAR encephalitis.
Topics: Algorithms; Antibodies; Clinical Trials as Topic; Diagnosis, Differential; Encephalitis; Female; Humans; Immunotherapy; Male; Models, Biological; Receptors, N-Methyl-D-Aspartate; Recovery of Function
PubMed: 21163445
DOI: 10.1016/S1474-4422(10)70253-2