277 results on '"Autoimmune Diseases of the Nervous System physiopathology"'
Search Results
52. Relapsing-remitting clinical course expands the phenotype of Aicardi-Goutières syndrome.
- Author
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Lambe J, Murphy OC, Mu W, Sondergaard Schatz K, Barañano KW, and Venkatesan A
- Subjects
- Adult, Female, Humans, Magnetic Resonance Imaging, Phenotype, Recurrence, Exome Sequencing, Young Adult, Autoimmune Diseases of the Nervous System diagnosis, Autoimmune Diseases of the Nervous System genetics, Autoimmune Diseases of the Nervous System physiopathology, Nervous System Malformations diagnosis, Nervous System Malformations genetics, Nervous System Malformations physiopathology, Ribonuclease H genetics
- Abstract
Aicardi-Goutières syndrome (AGS) is a rare and likely underdiagnosed genetic leukoencephalopathy, typically presenting in infancy with encephalopathy and characteristic neuroimaging features, with residual static neurological deficits. We describe a patient who, following an initial presentation at the age of 12 months in keeping with AGS, exhibited a highly atypical relapsing course of neurological symptoms in adulthood with essentially normal neuroimaging. Whole-exome sequencing confirmed a pathogenic RNASEH2B gene variant consistent with AGS. This case highlights the expanding phenotypes associated with AGS and the potential role of whole-exome sequencing in facilitating an increase in the rate of diagnosis., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.)
- Published
- 2020
- Full Text
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53. Treatment of Movement Disorder Emergencies in Autoimmune Encephalitis in the Neurosciences ICU.
- Author
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Ali F and Wijdicks EF
- Subjects
- Adrenergic alpha-Antagonists therapeutic use, Adrenergic beta-Antagonists therapeutic use, Analgesics, Opioid therapeutic use, Anticonvulsants therapeutic use, Antiparkinson Agents therapeutic use, Autoantibodies immunology, Autoimmune Diseases of the Nervous System complications, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System physiopathology, Benzodiazepines therapeutic use, Catatonia drug therapy, Catatonia etiology, Catatonia physiopathology, Chorea drug therapy, Chorea etiology, Chorea physiopathology, Critical Illness, Dopamine Antagonists therapeutic use, Dyskinesias drug therapy, Dyskinesias etiology, Dyskinesias physiopathology, Dystonia drug therapy, Dystonia etiology, Dystonia physiopathology, Emergencies, Encephalitis complications, Encephalitis immunology, Encephalitis physiopathology, Humans, Hypnotics and Sedatives therapeutic use, Immunoglobulins, Intravenous therapeutic use, Immunologic Factors therapeutic use, Intensive Care Units, Movement Disorders etiology, Movement Disorders physiopathology, Myoclonus drug therapy, Myoclonus etiology, Myoclonus physiopathology, Paraneoplastic Syndromes, Nervous System complications, Paraneoplastic Syndromes, Nervous System drug therapy, Paraneoplastic Syndromes, Nervous System immunology, Paraneoplastic Syndromes, Nervous System physiopathology, Plasmapheresis, Adrenal Cortex Hormones therapeutic use, Autoimmune Diseases of the Nervous System drug therapy, Cholinergic Antagonists therapeutic use, Dopamine Agents therapeutic use, Encephalitis drug therapy, Immunosuppressive Agents therapeutic use, Movement Disorders drug therapy, Neuromuscular Blocking Agents therapeutic use
- Abstract
Immune response against neuronal and glial cell surface and cytosolic antigens is an important cause of encephalitis. It may be triggered by activation of the immune system in response to an infection (para-infectious), cancer (paraneoplastic), or due to a patient's tendency toward autoimmunity. Antibodies directed toward neuronal cell surface antigens are directly pathogenic, whereas antibodies with intracellular targets may become pathogenic if the antigen is transiently exposed to the cell surface or via activation of cytotoxic T cells. Immune-mediated encephalitis is well recognized and may require intensive care due to status epilepticus, need for invasive ventilation, or dysautonomia. Patients with immune-mediated encephalitis may become critically ill and display clinically complex and challenging to treat movement disorders in over 80% of the cases (Zhang et al. in Neurocrit Care 29(2):264-272, 2018). Treatment options include immunotherapy and symptomatic agents affecting dopamine or acetylcholine neurotransmission. There has been no prior published guidance for management of these movement disorders for the intensivist. Herein, we discuss the immune-mediated encephalitis most likely to cause critical illness, clinical features and mechanisms of movement disorders and propose a management algorithm.
- Published
- 2020
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54. Unusual features of acute anti-myelin-associated glycoprotein polyneuropathy.
- Author
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Galassi G, Chiari A, Genovese M, Bedin R, and Malagoli M
- Subjects
- Autoantibodies immunology, Autoantigens immunology, Autoimmune Diseases of the Nervous System therapy, Globosides immunology, Humans, Male, Middle Aged, Plasma Exchange, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System physiopathology, Myelin-Associated Glycoprotein immunology
- Published
- 2020
- Full Text
- View/download PDF
55. Autoimmune Vestibulocerebellar Syndromes.
- Author
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Narayan RN, McKeon A, and Fife TD
- Subjects
- Humans, Syndrome, Autoantibodies blood, Autoimmune Diseases of the Nervous System diagnosis, Autoimmune Diseases of the Nervous System drug therapy, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System physiopathology, Cerebellar Diseases diagnosis, Cerebellar Diseases drug therapy, Cerebellar Diseases immunology, Cerebellar Diseases physiopathology, Immunologic Factors therapeutic use, Vestibular Diseases diagnosis, Vestibular Diseases drug therapy, Vestibular Diseases immunology, Vestibular Diseases physiopathology
- Abstract
Autoimmune disorders affecting the vestibular end organs, vestibular pathways, vestibular nuclei, and vestibulocerebellum are often underrecognized as a cause of chronic dizziness and ataxia. Autoantibodies specific for cell-surface, synaptic, and intracellular neural antigens serve as biomarkers of these disorders. This article describes the epidemiology, clinical presentation, diagnostic considerations, imaging findings, treatment, and prognosis of autoimmune disorders, in which the vestibulocerebellar syndrome is the main or presenting clinical presentation. Antibodies specific for intracellular antigenic targets described in the article are PCA-1 (Purkinje cell cytoplasmic antibody type 1, also known as anti-Yo), ANNA-1 (antinuclear neuronal antibody type 1, also known as anti-Hu), ANNA-2 (antinuclear neuronal antibody type 2, also known as anti-Ri), Ma1/2 (anti-Kelch-like 11/12 antibody), Kelch-like 11, amphiphysin, CV2 (collapsin response 2, also known as collapsin response mediator protein-5 [CRMP5]), VGCC (voltage-gated calcium channel), GAD65 (glutamic acid decarboxylase 65-kDa isoform), AP3B2 (adaptor protein 3B2, also known as anti-Nb), MAP1B (microtubule-associated protein 1B antibody, also known as anti-PCA-2), and neurochondrin antibodies. Antibodies targeting cell-surface or synaptic antigenic targets described in the article include DNER (delta/notchlike epidermal growth factor related receptor; antigen to anti-Tr), CASPR2 (contactin-associated proteinlike 2), septin-5, Homer-3, and mGluR1 (metabotropic glutamate receptor 1). The vestibulocerebellar presentation is largely indistinguishable among these conditions and is characterized by subacute onset of cerebellar symptoms over weeks to months. The diagnosis of autoimmune vestibulocerebellar syndromes is based on a combination of clinical and serological features, with a limited role for neuroimaging. Subtle eye movement abnormalities can be an early feature in many of these disorders, and therefore a meticulous vestibulo-ocular examination is essential for early and correct identification. Cancer occurrence and its type are variable and depend on the autoantibody detected and other cancer risk factors. Treatment comprises immunotherapy and cancer-directed therapy. Acute immunotherapies such as intravenous immunoglobulin, plasma exchange, and steroids are used in the initial phase, and the use of long-term immunosuppression such as rituximab may be necessary in relapsing cases. Outcomes are better if immunotherapy is started early. The neurologic prognosis depends on multiple factors., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)
- Published
- 2020
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56. Bilateral retinal pathology following a first-ever clinical episode of autoimmune optic neuritis.
- Author
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Wicki CA, Manogaran P, Simic T, Hanson JVM, and Schippling S
- Subjects
- Adult, Female, Humans, Longitudinal Studies, Male, Middle Aged, Retina diagnostic imaging, Retrospective Studies, Tomography, Optical Coherence, Vision Disorders etiology, Young Adult, Autoimmune Diseases of the Nervous System complications, Autoimmune Diseases of the Nervous System pathology, Autoimmune Diseases of the Nervous System physiopathology, Optic Neuritis complications, Optic Neuritis pathology, Optic Neuritis physiopathology, Retina pathology, Vision Disorders physiopathology, Visual Acuity physiology
- Abstract
Objective: This longitudinal study aimed to assess changes in retinal structure and visual function following a first-ever episode of acute optic neuritis (ON)., Methods: Clinical and optical coherence tomography (OCT) data obtained over a period of 12 months were retrospectively analyzed in 41 patients with a first-ever clinical episode of acute ON. OCT scans, high-contrast visual acuity (HCVA), and low-contrast visual acuity (LCVA) were acquired at baseline and at 1, 3, 6, and 12 months thereafter. Macular ganglion cell and inner plexiform layer (GCIP), peripapillary retinal nerve fiber layer (pRNFL), and macular inner nuclear layer (INL) thicknesses were assessed by OCT. Linear mixed-effects models were used to analyze OCT variables of ipsilateral ON and contralateral non-ON (NON) eyes over time., Results: The mean change of GCIP thickness in ON eyes was significant at all follow-up time points, with nearly 75% of the total reduction having occurred by month 1. In ON eyes, thinner GCIP thickness at month 1 correlated with lower LCVA at month 3. Mean pRNFL thickness in ON eyes differed significantly from NON eyes at all postbaseline time points. INL thickness was significantly increased in ON eyes (month 1) but also in contralateral NON eyes (month 12)., Conclusions: Retinal structural damage develops rapidly following acute ON and is associated with subsequent functional visual deficits. Our results also suggest bilateral retinal pathology following unilateral ON, possibly caused by subclinical involvement of the contralateral NON eyes. Moreover, our data may assist in clinical trial planning in studies targeting tissue damage in acute ON., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
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- 2020
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57. Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient.
- Author
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Cellucci T, Van Mater H, Graus F, Muscal E, Gallentine W, Klein-Gitelman MS, Benseler SM, Frankovich J, Gorman MP, Van Haren K, Dalmau J, and Dale RC
- Subjects
- Adolescent, Autoantibodies blood, Autoantibodies cerebrospinal fluid, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System metabolism, Autoimmune Diseases of the Nervous System physiopathology, Child, Consensus, Diagnosis, Differential, Encephalitis immunology, Encephalitis metabolism, Encephalitis physiopathology, Humans, Magnetic Resonance Imaging, Algorithms, Autoantibodies metabolism, Autoimmune Diseases of the Nervous System diagnosis, Encephalitis diagnosis, Practice Guidelines as Topic standards
- Abstract
Objective: Autoimmune encephalitis (AE) is an important and treatable cause of acute encephalitis. Diagnosis of AE in a developing child is challenging because of overlap in clinical presentations with other diseases and complexity of normal behavior changes. Existing diagnostic criteria for adult AE require modification to be applied to children, who differ from adults in their clinical presentations, paraclinical findings, autoantibody profiles, treatment response, and long-term outcomes., Methods: A subcommittee of the Autoimmune Encephalitis International Working Group collaborated through conference calls and email correspondence to consider the pediatric-specific approach to AE. The subcommittee reviewed the literature of relevant AE studies and sought additional input from other expert clinicians and researchers., Results: Existing consensus criteria for adult AE were refined for use in children. Provisional pediatric AE classification criteria and an algorithm to facilitate early diagnosis are proposed. There is also discussion about how to distinguish pediatric AE from conditions within the differential diagnosis., Conclusions: Diagnosing AE is based on the combination of a clinical history consistent with pediatric AE and supportive diagnostic testing, which includes but is not dependent on antibody testing. The proposed criteria and algorithm require validation in prospective pediatric cohorts., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
- Published
- 2020
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58. [Autoimmune autonomic ganglionopathy].
- Author
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Nakane S
- Subjects
- Animals, Humans, Immunotherapy methods, Autoantibodies, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System physiopathology, Autoimmune Diseases of the Nervous System therapy, Ganglia, Autonomic immunology, Receptors, Cholinergic immunology
- Abstract
Autoimmune autonomic ganglionopathy (AAG) is an acquired immune-mediated disorder of widespread autonomic failure. Approximately half of the patients with AAG have the autoantibodies against the neuronal nicotinic acetylcholine receptor (AChR) in autonomic ganglia. These ganglionic AChR antibodies have the potential to mediate the synaptic transmission in sympathetic, parasympathetic, and enteric ganglia. Therefore, seropositive AAG patients exhibit various autonomic symptoms. Extra-autonomic manifestations (coexistence with brain involvement, sensory disturbance, endocrine disorders, autoimmune diseases and tumors) are present in many patients with AAG. The nicotinic AChRs comprise a family of abundantly expressed ligand-gated cation channels found throughout the central and peripheral nervous systems. Moreover, limited manifestations of autoimmune dysautonomia including autoimmune gastrointestinal dysmotility are newly recognized clinical entity. Although combined immunomodulatory therapy is beneficial for almost all patients with AAG, several case reports of some AAG patients with small benefit exist. This review focuses on the recent progress in the clinical approaches of AAG and its related disorders involving the role of autoantibodies and clinical practice.
- Published
- 2019
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59. LGI-1 antibody encephalitis in a seven-year-old girl.
- Author
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Mir A, Thani Z, Bashir S, Ayed H, and Albaradie R
- Subjects
- Autoantibodies, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System physiopathology, Child, Electroencephalography, Encephalitis immunology, Encephalitis physiopathology, Female, Humans, Autoimmune Diseases of the Nervous System diagnosis, Encephalitis diagnosis, Intracellular Signaling Peptides and Proteins immunology
- Abstract
LGI-1 antibody encephalitis is a rare autoimmune limbic encephalitis which has been reported predominantly in adults. Seizures in LGI-1 antibody encephalitis exhibit significant semiological variability. Faciobrachial dystonic seizures are characteristically seen in this condition and have so far been described only in adults. Other seizure types have also been reported. We describe the case of a seven-year-old girl with LGI-1 limbic encephalitis who presented with acute new-onset seizures, and rapidly deteriorated over the course of a few weeks with very frequent seizures and encephalopathy, becoming non-verbal and non-ambulatory. The electroclinical presentation of this child with LGI-1 encephalitis makes this case unique and further highlights the importance of a high index of suspicion for diagnosis in young children. Early diagnosis can lead to prompt and appropriate treatment with immunotherapy, and potential harmful treatments such as pharmacological coma can be avoided. To the best of our knowledge, this is the youngest case ever reporter. [Published with video sequences].
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- 2019
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60. Amphiphysin-IgG autoimmune neuropathy: A recognizable clinicopathologic syndrome.
- Author
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Dubey D, Jitprapaikulsan J, Bi H, Do Campo RV, McKeon A, Pittock SJ, Engelstad JK, Mills JR, and Klein CJ
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Antinuclear immunology, Antibodies, Neoplasm, Autoimmune Diseases of the Nervous System epidemiology, Autoimmune Diseases of the Nervous System pathology, Autoimmune Diseases of the Nervous System physiopathology, Biopsy, Breast Neoplasms epidemiology, Comorbidity, Facial Nerve Diseases epidemiology, Facial Nerve Diseases immunology, Facial Nerve Diseases pathology, Facial Nerve Diseases physiopathology, Female, Humans, Hydrolases immunology, Immunoglobulin G immunology, Male, Microtubule-Associated Proteins immunology, Middle Aged, Nerve Tissue Proteins genetics, Pain, Peripheral Nerves immunology, Peripheral Nerves metabolism, Peripheral Nerves pathology, Polyradiculoneuropathy epidemiology, Polyradiculoneuropathy immunology, Polyradiculoneuropathy pathology, Polyradiculoneuropathy physiopathology, Stiff-Person Syndrome epidemiology, Syndrome, Autoantibodies immunology, Autoimmune Diseases of the Nervous System immunology, Nerve Tissue Proteins immunology
- Abstract
Objective: To define the clinicopathologic features of amphiphysin-immunoglobulin G (IgG)-mediated neuropathy., Methods: Patients examined at our institution from January 1, 1995, to September 30, 2018, with amphiphysin-IgG by indirect immunofluorescence and Western blot, were reviewed. Their phenotypes were compared to cases of coexisting collapsin response-mediator protein-5 (CRMP5)-IgG or anti-neuronal nuclear antibody type 1 (ANNA1-IgG) and CRMP5-IgG autoimmunity. Improvement in modified Rankin Scale (mRS) (≥1) on follow-up was considered a favorable outcome. Amphiphysin RNA expression was assessed in healthy nerves., Results: Fifty-three amphiphysin-IgG-positive cases were identified. Of 33 (60%) patients with neuropathy, 21 had amphiphysin-IgG alone, and 12 had coexisting autoantibodies (ANNA1-IgG, n = 8; CRMP5-IgG, n = 2; ANNA1-IgG and CRMP5-IgG, n = 2). The neuropathies in isolated amphiphysin-IgG autoimmunity included polyradiculoneuropathy (62%), diffuse sensory neuronopathy (35%), and facial neuropathy with gastroparesis (3%). Among these, pain (80%), breast cancer (63%), and CNS (57%) involvements commonly coexisted, and neuropathy frequently prompted breast cancer diagnosis (76%). Stiff-person spectrum disorder was the most common CNS accompaniment (45%). Nerve biopsies showed axonal loss (n = 6/6), subperineurial edema (n = 4/6), and CD4 predominant inflammation (n = 2/6). Median mRS score at last follow-up was 3.5; 58% of patients were immunotherapy-responsive. Patients with amphiphysin-IgG alone had more favorable immunotherapy response than patients with CRMP5-IgG polyneuropathy (n = 45) (44% vs 16%, p = 0.028, odds ratio 4.2, 95% confidence interval 1.1 to 15.5). Only 1/9 (11%) patients with amphiphysin-IgG with coexisting CRMP5-IgG or ANNA1-IgG had immunotherapy response. RNA amphiphysin expression occurred at low levels in nerve., Conclusion: Amphiphysin-IgG autoimmune neuropathy has a recognizable phenotype, is frequently immune responsive, and can prompt early diagnosis of breast cancer., (© 2019 American Academy of Neurology.)
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- 2019
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61. Teaching NeuroImages: 18 F-FDG-PET/SPM analysis in 3 different stages from a patient with LGI-1 autoimmune encephalitis.
- Author
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Shan W, Liu X, and Wang Q
- Subjects
- Autoantibodies blood, Autoantibodies cerebrospinal fluid, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System physiopathology, Brain Diseases immunology, Brain Diseases physiopathology, Female, Fluorodeoxyglucose F18, Humans, Intracellular Signaling Peptides and Proteins immunology, Middle Aged, Positron-Emission Tomography, Radiopharmaceuticals, Seizures physiopathology, Autoimmune Diseases of the Nervous System diagnostic imaging, Basal Ganglia diagnostic imaging, Brain Diseases diagnostic imaging, Temporal Lobe diagnostic imaging
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- 2019
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62. FDG-PET in Cotard syndrome before and after treatment: can functional brain imaging support a two-factor hypothesis of nihilistic delusions?
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Restrepo-Martínez M, Espinola-Nadurille M, Bayliss L, Díaz-Meneses I, Kerik NE, Mendez MF, and Ramírez-Bermúdez J
- Subjects
- Adult, Autoimmune Diseases of the Nervous System diagnostic imaging, Autoimmune Diseases of the Nervous System metabolism, Autoimmune Diseases of the Nervous System physiopathology, Autoimmune Diseases of the Nervous System therapy, Electroconvulsive Therapy, Encephalitis diagnostic imaging, Encephalitis metabolism, Encephalitis physiopathology, Encephalitis therapy, Fluorodeoxyglucose F18, Humans, Male, Young Adult, Cerebral Cortex diagnostic imaging, Cerebral Cortex metabolism, Cerebral Cortex physiopathology, Neuroimaging, Positron-Emission Tomography, Schizophrenia, Paranoid diagnostic imaging, Schizophrenia, Paranoid metabolism, Schizophrenia, Paranoid physiopathology, Schizophrenia, Paranoid therapy
- Abstract
Introduction: Cotard syndrome is a neuropsychiatric entity recognised by the presence of nihilistic delusions. Although different models have been proposed for the development of monothematic delusions, including Cotard syndrome, functional neuroanatomical models are lacking. Methods: A case report of a 19-year old male with autoimmune encephalitis and Cotard syndrome, in whom Positron Emission Tomography (
18 F-FDG-PET) scans were performed before and after successful treatment with electroconvulsive therapy (ECT), is presented. Literature review on brain imaging is provided to discuss a functional neuroanatomical model of Cotard syndrome, in accordance with the two-factor theory of delusions. Results: The patient's18 F-FDG-PET showed marked insular and prefrontal metabolic abnormalities. Except for insular hypometabolism, metabolic abnormalities improved after ECT. Previously reported structural neuroimaging studies in Cotard syndrome showed a predominance of right hemisphere lesions, in which frontal lobes were more frequently involved, followed by parietal and temporal lesions. Functional neuroimaging studies reported abnormalities in frontoparietal circuits as well as midline structures included in the "default mode network". Conclusions: Abnormalities in the functioning of the insular cortex and the prefrontal cortex could be related to the development of nihilistic delusions when a two-factor theory of delusions is considered.- Published
- 2019
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63. Atypical presentation of MOG-related disease: Slowly progressive behavioral and personality changes following a seizure.
- Author
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Yılmaz Ü, Edizer S, Songür ÇY, Güzin Y, and Durak FS
- Subjects
- Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System physiopathology, Child, Female, Humans, Autoimmune Diseases of the Nervous System diagnosis, Disease Progression, Myelin-Oligodendrocyte Glycoprotein immunology, Seizures physiopathology
- Abstract
Background: Myelin Oligodendrocyte Glycoprotein (MOG) antibodies-related disease is mainly presented with acute disseminated encephalomyelitis (ADEM), recurrent optic neuritis, and neuromyelitis optica spectrum disorders (NMOSDs), however the complete clinical spectrum has not yet been defined. We describe an unusual presentation of MOG- related disease. A previously well 10-year-old girl admitted with a focal onset seizure. Neurological examination, electroencephalography, and brain magnetic resonance imaging (MRI) were normal. Following seizure episode she developed gradually increased behavioral and personality changes during a period of 2.5 months. Neurological examination was unremarkable except for drowsiness and minimal ataxia on tandem walking. Repeated brain MRI revealed hazy and poorly demarcated lesions with gadolinium enhancement in the basal ganglia, supratentorial white matter, cerebral peduncles, cerebellum, and servical spinal cord. Cerebrospinal fluid analyses (CSF) revealed 10 lymphocytes /µL, normal protein concentration and IgG index, and negative oligoclonal bands. Auto-antibodies against N-methyl-d-aspartate receptor and CASPR2 in CSF, and antibodies against aquaporin 4 in serum were negative. Analysis with a cell-based assay identified high serum titer of MOG antibodies (1:320). Following IVIG therapy, the patient showed complete clinical recovery within a week with no further relaps for the following 6-month period., Conclusion: Slowly progressive behavioral and personality changes following a seizure may be a manifestation of MOG-related disease in children., (Copyright © 2019 Elsevier B.V. All rights reserved.)
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- 2019
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64. Early clinicopathologic description of nodoparanodopathy in the 19th century.
- Author
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Mathis S, Le Masson G, and Vallat JM
- Subjects
- Autoimmune Diseases of the Nervous System pathology, Autoimmune Diseases of the Nervous System physiopathology, History, 19th Century, Humans, Neurology history, Peripheral Nervous System Diseases pathology, Peripheral Nervous System Diseases physiopathology, Ranvier's Nodes pathology, Autoimmune Diseases of the Nervous System history, Peripheral Nervous System Diseases history
- Abstract
Nodoparanodopathy is a recent concept in the field of peripheral neuropathy, corresponding to peripheral nerve disorders stemming from an autoimmune attack directed and limited to the nodal region. This concept was identified using modern techniques of electrophysiology, immunology, and pathology (including electron microscopy). We present here what we believe to be the earlier well-documented case of nodoparanodopathy in the medical literature, based on an article written by Samuel Gilbert Webber (1838-1926) in 1884., (© 2019 American Academy of Neurology.)
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- 2019
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65. Neurological autoimmune disorders with prominent gastrointestinal manifestations: A review of presentation, evaluation, and treatment.
- Author
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Blackburn KM, Kubiliun M, Harris S, and Vernino S
- Subjects
- Adult, Aged, Antibodies, Antinuclear immunology, Antibodies, Neoplasm, Aquaporin 4 immunology, Area Postrema physiopathology, Autoantibodies immunology, Autoimmune Diseases of the Nervous System complications, Autoimmune Diseases of the Nervous System drug therapy, Autoimmune Diseases of the Nervous System immunology, Autonomic Nervous System Diseases complications, Autonomic Nervous System Diseases drug therapy, Autonomic Nervous System Diseases immunology, Autonomic Nervous System Diseases physiopathology, Brain diagnostic imaging, Diarrhea etiology, Diarrhea immunology, Diarrhea physiopathology, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases immunology, Female, Gastrointestinal Diseases etiology, Gastrointestinal Diseases immunology, Gastroparesis etiology, Gastroparesis immunology, Gastroparesis physiopathology, Humans, Immunosuppressive Agents therapeutic use, Intestinal Pseudo-Obstruction complications, Intestinal Pseudo-Obstruction drug therapy, Intestinal Pseudo-Obstruction immunology, Intestinal Pseudo-Obstruction physiopathology, Male, Middle Aged, Nausea etiology, Nausea immunology, Nausea physiopathology, Nerve Tissue Proteins immunology, Neuromyelitis Optica complications, Neuromyelitis Optica drug therapy, Neuromyelitis Optica immunology, Neuromyelitis Optica physiopathology, Paraneoplastic Syndromes, Nervous System complications, Paraneoplastic Syndromes, Nervous System drug therapy, Paraneoplastic Syndromes, Nervous System immunology, Paraneoplastic Syndromes, Nervous System physiopathology, Potassium Channels immunology, Weight Loss, Autoimmune Diseases of the Nervous System physiopathology, Gastrointestinal Diseases physiopathology
- Abstract
Background: The identification of autoantibodies directed against neuronal antigens has led to the recognition of a wide spectrum of neurological autoimmune disorders (NAD). With timely recognition and treatment, many patients with NAD see rapid improvement. Symptoms associated with NAD can be diverse and are determined by the regions of the nervous system affected. In addition to neurological symptoms, a number of these disorders present with prominent gastrointestinal (GI) manifestations such as nausea, diarrhea, weight loss, and gastroparesis prompting an initial evaluation by gastroenterologists., Purpose: This review provides a general overview of autoantibodies within the nervous system, focusing on three scenarios in which nervous system autoimmunity may initially present with gut symptoms. A general approach to evaluation and treatment, including antibody testing, will be reviewed., (© 2019 John Wiley & Sons Ltd.)
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- 2019
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66. Neurochondrin neurological autoimmunity.
- Author
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Shelly S, Kryzer TJ, Komorowski L, Miske R, Anderson MD, Flanagan EP, Hinson SR, Lennon VA, Pittock SJ, and McKeon A
- Subjects
- Adult, Aged, Animals, Female, Humans, Male, Mice, Middle Aged, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System pathology, Autoimmune Diseases of the Nervous System physiopathology, Autoimmunity immunology, Encephalitis immunology, Encephalitis pathology, Encephalitis physiopathology, Nerve Tissue Proteins immunology
- Abstract
Objectives: To describe the neurologic spectrum and treatment outcomes for neurochondrin-IgG positive cases identified serologically in the Mayo Clinic Neuroimmunology Laboratory., Methods: Archived serum and CSF specimens previously scored positive for IgGs that stained mouse hippocampal tissue in a nonuniform synaptic pattern by immunofluorescence assay (89 among 616,025 screened, 1993-2019) were reevaluated. Antibody characterization experiments revealed specificity for neurochondrin, confirmed by recombinant protein assays., Results: IgG in serum (9) or CSF (4) from 8 patients yielded identical neuron-restricted CNS patterns, most pronounced in hippocampus (stratum lucidum in particular), cerebellum (Purkinje cells and molecular layer), and amygdala. All were neurochondrin-IgG positive. Five were women; median symptom onset age was 43 years (range, 30-69). Of 7 with clinical data, 6 presented with rapidly progressive cerebellar ataxia, brainstem signs, or both; 1 had isolated unexplained psychosis 1 year prior. Five of 6 had cerebellar signs, 4 with additional brainstem symptoms or signs (eye movement abnormalities, 3; dysphagia, 2; nausea and vomiting, 1). One patient with brainstem signs (vocal cord paralysis and VII nerve palsy) had accompanying myelopathy (longitudinally extensive abnormality on MRI; aquaporin-4-IgG and myelin oligodendrocyte glycoprotein-IgG negative). The 7th patient had small fiber neuropathy only. Just 1 of 7 had contemporaneous cancer (uterine). Six patients with ataxia or brainstem signs received immunotherapy, but just 1 remained ambulatory. At last follow-up, 5 had MRI evidence of severe cerebellar atrophy., Conclusion: In our series, neurochondrin autoimmunity was usually accompanied by a nonparaneoplastic rapidly progressive rhombencephalitis with poor neurologic outcomes. Other phenotypes and occasional paraneoplastic causes may occur., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
- Published
- 2019
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67. Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Following Herpes Simplex Virus Encephalitis in a Pediatric Patient.
- Author
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Handoko M, Hong W, Espineli E, Saxena K, Muscal E, and Risen S
- Subjects
- Autoimmune Diseases of the Nervous System cerebrospinal fluid, Autoimmune Diseases of the Nervous System physiopathology, Child, Humans, Male, Meningoencephalitis cerebrospinal fluid, Meningoencephalitis physiopathology, Astrocytes pathology, Autoantibodies cerebrospinal fluid, Autoimmune Diseases of the Nervous System etiology, Encephalitis, Herpes Simplex complications, Glial Fibrillary Acidic Protein immunology, Meningoencephalitis etiology
- Published
- 2019
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68. Peculiar EEG signatures, ictal drinking and long-term follow-up in anti-LGI1 encephalitis.
- Author
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Vogrig A, Pauletto G, Lettieri C, Valente M, and Gigli GL
- Subjects
- Autoantibodies blood, Autoantibodies cerebrospinal fluid, Autoimmune Diseases of the Nervous System complications, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System physiopathology, Biomarkers, Electroencephalography, Encephalitis complications, Encephalitis immunology, Encephalitis physiopathology, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Middle Aged, Seizures diagnosis, Seizures etiology, Seizures physiopathology, Autoimmune Diseases of the Nervous System diagnosis, Encephalitis diagnosis, Intracellular Signaling Peptides and Proteins immunology
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- 2019
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69. Autoimmune autonomic neuropathies and ganglionopathies: epidemiology, pathophysiology, and therapeutic advances.
- Author
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Golden EP and Vernino S
- Subjects
- Autoimmune Diseases of the Nervous System therapy, Guillain-Barre Syndrome therapy, Humans, Immunotherapy methods, Autoimmune Diseases of the Nervous System epidemiology, Autoimmune Diseases of the Nervous System physiopathology, Ganglia, Autonomic physiopathology, Guillain-Barre Syndrome epidemiology, Guillain-Barre Syndrome physiopathology
- Abstract
Autonomic disorders can be the result of autoimmunity. The classic, well-characterized example is autoimmune autonomic ganglionopathy (AAG), in which antibodies against the ganglionic nicotinic acetylcholine receptor impair autonomic transmission, causing autonomic failure, which responds to immunotherapy. However, a number of other autoimmune disorders cause autonomic failure through a variety of mechanisms. In this article, we review autoimmune disorders causing impairment of the peripheral autonomic nervous system (ganglia and nerves), including AAG, other autoimmune autonomic neuropathies, paraneoplastic autonomic neuropathies, and neuromuscular and rheumatologic diseases with autonomic symptomatology. Awareness of primary autoimmune autonomic disorders and the autonomic manifestations of other autoimmune diseases promotes timely diagnosis and appropriate management, including supportive care for unpleasant or dangerous autonomic dysfunction, a search for underlying malignancy when indicated, and the use of immunotherapy when appropriate. A better understanding of the underlying pathophysiology aids in the judicious use and selection of immunotherapy.
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- 2019
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70. Transfer of the Experimental Autoimmune Glaucoma Model from Rats to Mice-New Options to Study Glaucoma Disease.
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Reinehr S, Reinhard J, Wiemann S, Hesse K, Voss C, Gandej M, Dick HB, Faissner A, and Joachim SC
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- Animals, Autoantibodies immunology, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System physiopathology, Disease Models, Animal, Glaucoma immunology, Glaucoma physiopathology, Intraocular Pressure, Mice, Optic Nerve immunology, Optic Nerve pathology, Retina immunology, Synapses pathology, Autoantibodies toxicity, Autoimmune Diseases of the Nervous System pathology, Glaucoma pathology, Retina pathology
- Abstract
Studies have suggested an involvement of the immune system in glaucoma. Hence, a rat experimental autoimmune glaucoma model (EAG) was developed to investigate the role of the immune response. Here, we transferred this model into mice. Either 0.8 mg/mL of the optic nerve antigen homogenate (ONA; ONA 0.8) or 1.0 mg/mL ONA (ONA 1.0) were injected in 129/Sv mice. Controls received sodium chloride. Before and 6 weeks after immunization, the intraocular pressure (IOP) was measured. At 6 weeks, retinal neurons, glia cells, and synapses were analyzed via immunohistology and quantitative real-time PCR (RT-qPCR). Additionally, optic nerves were examined. The IOP stayed in the normal physiological range throughout the study ( p > 0.05). A significant reduction of retinal ganglion cells (RGCs) was noted in both immunized groups ( p < 0.001). Remodeling of glutamatergic and GABAergic synapses was seen in ONA 1.0 retinas. Furthermore, both ONA groups revealed optic nerve degeneration and macrogliosis (all: p < 0.001). An increase of activated microglia was noted in ONA retinas and optic nerves ( p < 0.05). Both ONA concentrations led to RGC loss and optic nerve degeneration. Therefore, the EAG model was successfully transferred from rats to mice. In further studies, transgenic knockout mice can be used to investigate the pathomechanisms of glaucoma more precisely., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
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- 2019
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71. Electroclinical insights into autoimmune epilepsy.
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Gillinder L, Papacostas J, and Dionisio S
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- Adult, Autoimmune Diseases of the Nervous System drug therapy, Autoimmune Diseases of the Nervous System physiopathology, Electrodes, Implanted, Epilepsy drug therapy, Epilepsy physiopathology, Female, Glucocorticoids administration & dosage, Humans, Immunologic Factors administration & dosage, Autoimmune Diseases of the Nervous System diagnosis, Electroencephalography instrumentation, Electroencephalography methods, Epilepsy diagnosis, Stereotaxic Techniques instrumentation
- Abstract
Purpose: Chronic autoimmune epilepsy is an increasingly recognised entity however its clinical and electrographic features remain poorly understood. We present a case undergoing diagnostic Stereo-electroencephalography implantation that was found to have a multifocal perisylvian epilepsy with unique electrographic features and is now seizure free with immunotherapy., Methods: The patient had antibody negative refractory perisylvian epilepsy and underwent implantation of the perisylvian-temporal networks. Immunomodulatory treatment was administered during SEEG., Results: SEEG demonstrated a multifocal perisylvian epilepsy with strong involvement of the posterior insula. There was almost continuous spiking seen interictally from multiple foci within the right hemisphere and independent seizures were generated from 5 locations. After treatment with intravenous methylprednisone and immunoglobulin during SEEG, spiking and seizures terminated while still off anti-seizure medications. The patient remains seizure free on immunotherapy., Conclusion: This case highlights the importance of considering autoimmunity in the differential diagnosis of refractory epilepsy, especially perisylvian epilepsy. It also highlights the need to define a clinical phenotype associated with autoantibodies in epilepsy, as there are likely many cases who are not positive for one of the commercially available tests. This case also provides insights into the possible features of an electroclinical syndrome associated with autoimmunity., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)
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- 2019
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72. [Aicardi-Goutières syndrome: Phenotypic and genetic spectrum in a series of three cases].
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Moreno Medinilla EE, Villagrán García M, Mora Ramírez MD, Calvo Medina R, and Martínez Antón JL
- Subjects
- Autoimmune Diseases of the Nervous System genetics, Child, Child, Preschool, Female, Humans, Male, Nervous System Malformations genetics, Phenotype, Autoimmune Diseases of the Nervous System physiopathology, Nervous System Malformations physiopathology
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- 2019
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73. Pediatric glial fibrillary acidic protein meningoencephalomyelitis: A case report and review of the literature.
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Francisco C, Meddles K, and Waubant E
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- Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System pathology, Autoimmune Diseases of the Nervous System physiopathology, Child, Female, Humans, Magnetic Resonance Imaging, Meningoencephalitis immunology, Meningoencephalitis pathology, Meningoencephalitis physiopathology, Autoantibodies immunology, Autoimmune Diseases of the Nervous System diagnosis, Glial Fibrillary Acidic Protein immunology, Meningoencephalitis diagnosis
- Abstract
A novel autoantibody, glial fibrillary acidic protein (GFAP)-IgG, has recently been associated with cases of meningoencephalomyelitis. This entity is still being unraveled. Very few pediatric patients have been identified; thus, the clinical, biological and imaging phenotype remains to be defined. Herein we describe the clinical course of a 6-year-old patient initially suspected to have a demyelinating disease but ultimately diagnosed with GFAP-IgG positive autoimmune meningoencephalomyelitis. We also provide a review of the literature regarding this novel entity., (Published by Elsevier B.V.)
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- 2019
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74. Autoimmune Encephalitides and Rapidly Progressive Dementias.
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Wesley SF and Ferguson D
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- Autoimmune Diseases of the Nervous System drug therapy, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System physiopathology, Dementia drug therapy, Dementia immunology, Dementia physiopathology, Encephalitis drug therapy, Encephalitis immunology, Encephalitis physiopathology, Humans, Autoimmune Diseases of the Nervous System diagnosis, Dementia diagnosis, Disease Progression, Encephalitis diagnosis
- Abstract
Rapidly progressive dementia (RPD) or cognitive decline is a common presenting complaint in neurology. While primary dementia is often a concern, other forms of reversible dementia must be thoroughly considered. This article focuses on the growing field of autoimmune encephalitis (AE) as it pertains to the differential diagnostic considerations in a work-up for RPD. Understanding clues in the history and examination is the first step in identifying patients with a potential autoimmune cause for RPD. While testing for infectious and toxic-metabolic etiologies is commonly preformed, it is necessary to consider early ancillary testing for AE in appropriate cases of RPD. Autoantibody testing in the spinal fluid and serum, brain imaging, and electroencephalography all form the first line of investigations for AE. Treatment options and strategies depend on the AE subtype and a number of individual patient considerations., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)
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- 2019
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75. Typical clinical and imaging manifestations of encephalitis with anti-γ-aminobutyric acid B receptor antibodies: clinical experience and a literature review.
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Si Z, Wang A, Liu J, Zhang Z, and Hu K
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- Adult, Aged, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System pathology, Autoimmune Diseases of the Nervous System physiopathology, Encephalitis immunology, Encephalitis pathology, Encephalitis physiopathology, Female, Humans, Male, Middle Aged, Retrospective Studies, Young Adult, Autoantibodies blood, Autoantibodies cerebrospinal fluid, Autoimmune Diseases of the Nervous System diagnosis, Encephalitis diagnosis, Receptors, GABA-B immunology
- Abstract
Objective: To explore the clinical, imaging, and electroencephalogram (EEG) findings, as well as the treatment and prognosis of five patients with anti-γ-aminobutyric acid B receptor (GABA
B R) encephalitis and review the current literature to gain a deeper understanding and improve the clinical diagnostic ability of the disease., Methods: Clinical data such as blood examination, imaging, computed tomography (CT), EEG, and magnetic resonance imaging (MRI) findings from five patients with anti-GABAB R encephalitis were retrospectively analyzed., Results: Based on the imaging data, autoimmune encephalitis with anti-GABAB R antibodies displayed subacute onset of episodic memory loss, seizures, and confusion, in addition to signal changes in the medial temporal lobe and/or hippocampus. Anti-GABAB R antibodies were found in blood and cerebrospinal fluid (CSF) in all five patients, although the CSF leukocyte count and the levels of protein, sugar, and chloride showed no obvious abnormalities. On MRI, only two patients presented with abnormal signals in the medial temporal lobe and/or hippocampus. The EEG showed a slow wave rhythm in all five patients. After treatment with methylprednisolone pulse therapy combined with antiepileptic treatment, all five patients recovered well, without any complications., Conclusions: Autoimmune encephalitis with anti-GABAB R antibodies may be a severe and refractory disease. Anti-GABAB R antibodies tested in CSF and serum play a crucial role in the definitive diagnosis and treatment of autoimmune encephalitis. Early treatment is of vital importance to avoid serious complications and neurological sequelae.- Published
- 2019
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76. Development of the clinical assessment scale in autoimmune encephalitis.
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Lim JA, Lee ST, Moon J, Jun JS, Kim TJ, Shin YW, Abdullah S, Byun JI, Sunwoo JS, Kim KT, Yang TW, Lee WJ, Moon HJ, Kim DW, Lim BC, Cho YW, Yang TH, Kim HJ, Kim YS, Koo YS, Park B, Jung KH, Kim M, Park KI, Jung KY, Chu K, and Lee SK
- Subjects
- Adolescent, Adult, Aged, Aggression psychology, Anti-N-Methyl-D-Aspartate Receptor Encephalitis complications, Anti-N-Methyl-D-Aspartate Receptor Encephalitis physiopathology, Anti-N-Methyl-D-Aspartate Receptor Encephalitis psychology, Ataxia etiology, Ataxia physiopathology, Autoimmune Diseases complications, Autoimmune Diseases physiopathology, Autoimmune Diseases psychology, Autoimmune Diseases of the Nervous System complications, Delusions psychology, Dyskinesias etiology, Dyskinesias physiopathology, Dystonia etiology, Dystonia physiopathology, Encephalitis complications, Encephalomyelitis, Acute Disseminated complications, Encephalomyelitis, Acute Disseminated physiopathology, Encephalomyelitis, Acute Disseminated psychology, Female, Gait Disorders, Neurologic etiology, Gait Disorders, Neurologic physiopathology, Hallucinations psychology, Humans, Language Disorders etiology, Language Disorders physiopathology, Limbic Encephalitis complications, Limbic Encephalitis physiopathology, Limbic Encephalitis psychology, Male, Memory Disorders etiology, Memory Disorders physiopathology, Middle Aged, Muscle Weakness etiology, Muscle Weakness physiopathology, Reproducibility of Results, Seizures etiology, Seizures physiopathology, Severity of Illness Index, Young Adult, Autoimmune Diseases of the Nervous System physiopathology, Autoimmune Diseases of the Nervous System psychology, Encephalitis physiopathology, Encephalitis psychology
- Abstract
Objective: There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to verify the reliability and validity of the developed scale., Methods: The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38)., Results: A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient [ICC] = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p < 0.001), and had acceptable internal consistency (Cronbach α = 0.88). Additionally, in the validation cohort, the scale showed high interobserver reliability (ICC = 0.99) and internal consistency (Cronbach α = 0.92)., Interpretation: CASE is a novel clinical scale for AE with a high level of clinimetric properties. It would be suitable for application in clinical practice and might help overcome the limitations of current outcome scales for AE. ANN NEUROL 2019;85:352-358., (© 2019 American Neurological Association.)
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- 2019
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77. Patient characteristics and outcome associations in AMPA receptor encephalitis.
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Laurido-Soto O, Brier MR, Simon LE, McCullough A, Bucelli RC, and Day GS
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- Adolescent, Adult, Aged, Aged, 80 and over, Humans, Male, Middle Aged, Neuroimaging, Young Adult, Autoimmune Diseases of the Nervous System diagnostic imaging, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System pathology, Autoimmune Diseases of the Nervous System physiopathology, Encephalitis diagnostic imaging, Encephalitis immunology, Encephalitis pathology, Encephalitis physiopathology, Receptors, Glutamate immunology
- Abstract
Antibody-mediated encephalitis defines a class of diseases wherein antibodies directed at cell-surface receptors are associated with behavioral and cognitive disturbances. One such recently described encephalitis is due to antibodies directed at alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR). This entity is exceptionally rare and its clinical phenotype incompletely described. We present findings from two cases of AMPAR encephalitis that exemplify variability in the disease spectrum, and summarize findings in published cases derived from a systematic literature review. When all patients are considered together, the presence of psychiatric symptoms at presentation portended a poor outcome and was associated with the presence of a tumor. Furthermore, we provide evidence to suggest that the topography of magnetic resonance imaging abnormalities in reported cases mirrors the distribution of AMPARs in the human brain. The potential for neurological improvement following immunomodulatory therapy together with the favorable outcome reported in most cases emphasizes the importance of testing for autoantibodies against neuronal cell-surface proteins, including AMPAR, in patients with clinical and neuroimaging findings suggestive of autoimmune encephalitis. Close attention to the clinical phenotype may inform the presence of malignancy and long-term prognosis.
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- 2019
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78. A Rasmussen encephalitis, autoimmune encephalitis, and mitochondrial disease mimicker: expanding the DNM1L-associated intractable epilepsy and encephalopathy phenotype.
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Nolan DA, Chen B, Michon AM, Salatka E, and Arndt D
- Subjects
- Adolescent, Disease Progression, Dynamins, Fatal Outcome, Female, Humans, Autoimmune Diseases of the Nervous System diagnosis, Autoimmune Diseases of the Nervous System genetics, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System physiopathology, Drug Resistant Epilepsy diagnosis, Drug Resistant Epilepsy genetics, Drug Resistant Epilepsy immunology, Drug Resistant Epilepsy physiopathology, Encephalitis diagnosis, Encephalitis genetics, Encephalitis immunology, Encephalitis physiopathology, GTP Phosphohydrolases genetics, Microtubule-Associated Proteins genetics, Mitochondrial Proteins genetics
- Abstract
Dynamin-1-like protein (DNM1L) gene variants have been linked to childhood refractory epilepsy, developmental delay, encephalopathy, microcephaly, and progressive diffuse cerebral atrophy. However, only a few cases have been reported in the literature and there is still a limited amount of information about the symptomatology and pathophysiology associated with pathogenic variants of DNM1L. We report a 10-year-old girl with a one-year history of mild learning disorder and absence seizures who presented with new-onset focal status epilepticus which progressed to severe encephalopathy and asymmetric hemispheric cerebral atrophy. Differential diagnosis included mitochondrial disease, Rasmussen's encephalitis, and autoimmune encephalitis. Disease progressed from one hemisphere to the other despite anti-seizure medications, hemispherectomy, vagus nerve stimulator, ketogenic diet, and immunomodulators. Continued cerebral atrophy and refractory seizures evolved until death four years after initial presentation. Post-mortem whole-exome sequencing revealed a pathogenic DNM1L variant. This paper presents a novel case of adolescent-onset DNM1L-related intractable epilepsy and encephalopathy.
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- 2019
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79. Clinical Heterogeneity in Patients with Glutamate Decarboxylase Antibody.
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Huang J, Li H, Zhou R, Huang W, Lin W, Chen T, and Long Y
- Subjects
- Adult, Autoimmune Diseases of the Nervous System diagnostic imaging, Autoimmune Diseases of the Nervous System immunology, Brain diagnostic imaging, Breast Neoplasms metabolism, Encephalitis diagnostic imaging, Encephalitis immunology, Encephalitis physiopathology, Female, Glutamate Decarboxylase metabolism, Humans, Magnetic Resonance Imaging, Middle Aged, Muscle Cramp immunology, Muscle Cramp physiopathology, Myelitis immunology, Myelitis physiopathology, Paraneoplastic Syndromes, Nervous System diagnostic imaging, Paraneoplastic Syndromes, Nervous System immunology, Paresthesia immunology, Paresthesia physiopathology, Recurrence, Retrospective Studies, Stiff-Person Syndrome immunology, Stiff-Person Syndrome physiopathology, Thymus Neoplasms metabolism, Vision Disorders immunology, Vision Disorders physiopathology, Young Adult, Autoantibodies immunology, Autoimmune Diseases of the Nervous System physiopathology, Glutamate Decarboxylase immunology, Paraneoplastic Syndromes, Nervous System physiopathology
- Abstract
Objective: To explore the diversity and clinical features of anti-glutamate decarboxylase (GAD) antibody-associated neurological diseases., Methods: Clinical data of a series of 5 patients positive for anti-GAD antibodies were retrospectively analyzed., Results: All 5 patients were female, with a median age of 41.5 years (range 19-60 years). Their neurological symptoms included stiff-person syndrome (SPS), encephalitis, myelitis, cramp, visual loss, and paresthesia. Three patients (60%) were diagnosed with tumors, 2 cases of thymic tumor and 1 of breast cancer. On immunohistochemistry for tumor pathology, expression of GAD65 was found only in 1 patient. Four patients (80%) had abnormal brain MRI findings. All patients received immunotherapy and improved significantly after treatment, but 4 (80%) then experienced a relapse., Conclusions: Neurological manifestations in anti-GAD-positive patients are diverse and include SPS, encephalitis, myelitis, cramp, visual loss, and paresthesia., (© 2019 S. Karger AG, Basel.)
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- 2019
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80. Parkinsonism in autoimmune diseases.
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Barba C and Alexopoulos H
- Subjects
- Autoimmune Diseases of the Nervous System physiopathology, Central Nervous System Infections physiopathology, Encephalitis physiopathology, Humans, Paraneoplastic Syndromes, Nervous System physiopathology, Parkinsonian Disorders physiopathology, Rheumatic Diseases physiopathology, Autoimmune Diseases of the Nervous System complications, Central Nervous System Infections complications, Encephalitis complications, Paraneoplastic Syndromes, Nervous System complications, Parkinsonian Disorders etiology, Rheumatic Diseases complications
- Abstract
Parkinsonism can be manifested and complicate either systemic or organ-specific autoimmune diseases. Even though it is a rare co-morbidity, it merits attention from clinicians as it affects the quality of life of patients. In systemic autoimmune diseases such as systemic lupus erythematosus, antiphospholipid syndrome and Sjogren's syndrome reported cases of parkinsonism are attributed to the underlying disease and its mechanisms, whether this is brain vasculitis or immune complexes. Regarding antibody-mediated autoimmune neurological disorders, parkinsonism is, in most cases, a manifestation within the spectrum of each disorder and is attributed to the action of humoral and cellular immunity in brain regions such as the basal ganglia. Depending on the pathophysiology, immunotherapy can be effective, while Parkinson's specific therapies are usually less effective., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2019
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81. The role of thymic tolerance in CNS autoimmune disease.
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Handel AE, Irani SR, and Holländer GA
- Subjects
- Animals, Humans, Thymus Gland immunology, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System pathology, Autoimmune Diseases of the Nervous System physiopathology, Immune Tolerance physiology, T-Lymphocytes, Regulatory, Thymus Gland pathology
- Abstract
The contributions of the peripheral adaptive and innate immune systems to CNS autoimmunity have been extensively studied. However, the role of thymic selection in these conditions is much less well understood. The thymus is the primary lymphoid organ for the generation of T cells; thymic mechanisms ensure that cells with an overt autoreactive specificity are eliminated before they emigrate to the periphery and control the generation of thymic regulatory T cells. Evidence from animal studies demonstrates that thymic T cell selection is important for establishing tolerance to autoantigens. However, there is a considerable knowledge gap regarding the role of thymic selection in autoimmune conditions of the human CNS. In this Review, we critically examine the current body of experimental evidence for the contribution of thymic tolerance to CNS autoimmune diseases. An understanding of why dysfunction of either thymic or peripheral tolerance mechanisms rarely leads to CNS inflammation is currently lacking. We examine the potential of de novo T cell formation and thymic selection as novel therapeutic avenues and highlight areas for future study that are likely to make these targets the focus of future treatments.
- Published
- 2018
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82. Extreme delta brush and distinctive imaging in a pediatric patient with autoimmune GFAP astrocytopathy.
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Theroux LM, Goodkin HP, Heinan KC, Quigg M, and Brenton JN
- Subjects
- Adolescent, Female, Humans, Magnetic Resonance Imaging, Astrocytes immunology, Astrocytes pathology, Autoimmune Diseases of the Nervous System diagnostic imaging, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System physiopathology, Delta Rhythm physiology, Encephalitis diagnostic imaging, Encephalitis immunology, Encephalitis physiopathology, Glial Fibrillary Acidic Protein immunology, Meningitis diagnostic imaging, Meningitis immunology, Meningitis physiopathology, Myelitis diagnostic imaging, Myelitis immunology, Myelitis physiopathology
- Abstract
Autoimmune encephalitis has been increasingly recognized within the pediatric population, and the number of implicated autoantibodies continues to grow. The identification of characteristic clinical and paraclinical features helps direct the evaluation and increases the likelihood of making a definitive diagnosis of a specific antibody-mediated encephalitis. The finding of extreme delta brush on electroencephalogram (EEG) has been suggested to serve as a clinical clue to the diagnosis of anti-NMDA-R encephalitis. Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a recently described antibody-mediated meningoencephalomyelitis, reported almost exclusively in adult patients. We report a case of autoimmune GFAP astrocytopathy in a pediatric patient with extreme delta brush pattern on EEG, negative anti-NMDA-R antibodies, and distinctive MRI findings. The findings reported herein should prompt clinicians to consider the diagnosis of autoimmune GFAP astrocytopathy in patients with suspected autoimmune encephalitis., (Copyright © 2018 Elsevier B.V. All rights reserved.)
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- 2018
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83. Extreme delta - With or without brushes: A potential surrogate marker of disease activity in anti-NMDA-receptor encephalitis.
- Author
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Steriade C, Hantus S, Moosa ANV, and Rae-Grant AD
- Subjects
- Adult, Autoantibodies cerebrospinal fluid, Autoimmune Diseases of the Nervous System diagnosis, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System therapy, Encephalitis diagnosis, Encephalitis immunology, Encephalitis therapy, Female, Humans, Immunotherapy, Male, Autoimmune Diseases of the Nervous System physiopathology, Delta Rhythm, Encephalitis physiopathology, Receptors, N-Methyl-D-Aspartate immunology
- Abstract
Objective: Anti-NMDA receptor encephalitis (NMDARE) may not respond to first line immunotherapy. Biomarkers to track disease course and guide escalation of immunotherapy are needed. We describe the evolution of EEG in four patients with NMDARE requiring prolonged intensive care., Methods: Within a database of 121 patients with immune-mediated neurological disorders, ten with NMDARE were retrospectively identified. Four patients did not respond to first line immunotherapy. Continuous EEG was reviewed and correlated with clinical status and treatment., Results: Intermittent polymorphic delta slowing was present in all patients. Generalized rhythmic delta occupied increasing proportion of the EEG as disease progressed, at times with superimposed beta. The institution of second line immunotherapy was followed by progressive decrease in rhythmic delta, predating clinical improvement. In one patient who did not respond to second line immunotherapy, rhythmic delta continued to occupy a majority of the recording. The extreme delta pattern was not seen in a comparison cohort of patients with autoimmune encephalitis without anti-NMDA-R antibodies., Conclusions: Extreme delta, with or without brushes, increases with progression of NMDARE, responds to escalation of immunotherapy, predating clinical improvement, and is likely specific to NMDA-R antibodies., Significance: Extreme delta may be a surrogate marker of disease activity in NMDARE refractory to first line immunotherapy., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)
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- 2018
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84. Contactin-associated protein-like 2, a protein of the neurexin family involved in several human diseases.
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Saint-Martin M, Joubert B, Pellier-Monnin V, Pascual O, Noraz N, and Honnorat J
- Subjects
- Action Potentials, Animals, Autoimmune Diseases of the Nervous System genetics, Axons physiology, Disease Models, Animal, Humans, Membrane Proteins genetics, Nerve Tissue Proteins genetics, Neurodevelopmental Disorders genetics, Autoimmune Diseases of the Nervous System physiopathology, Brain physiopathology, Membrane Proteins physiology, Nerve Tissue Proteins physiology, Neurodevelopmental Disorders physiopathology
- Abstract
Contactin-associated protein-like 2 (CASPR2) is a cell adhesion protein of the neurexin family. Proteins of this family have been shown to play a role in the development of the nervous system, in synaptic functions, and in neurological diseases. Over recent years, CASPR2 function has gained an increasing interest as demonstrated by the growing number of publications. Here, we gather published data to comprehensively review CASPR2 functions within the nervous system in relation to CASPR2-related diseases in humans. On the one hand, studies on Cntnap2 (coding for CASPR2) knockout mice revealed its role during development, especially, in setting-up the inhibitory network. Consistent with this result, mutations in the CNTNAP2 gene coding for CASPR2 in human have been identified in neurodevelopmental disorders such as autism, intellectual disability, and epilepsy. On the other hand, CASPR2 was shown to play a role beyond development, in the localization of voltage-gated potassium channel (VGKC) complex that is composed of TAG-1, Kv1.1, and Kv1.2. This complex was found in several subcellular compartments essential for action potential propagation: the node of Ranvier, the axon initial segment, and the synapse. In line with a role of CASPR2 in the mature nervous system, neurological autoimmune diseases have been described in patients without neurodevelopmental disorders but with antibodies directed against CASPR2. These autoimmune diseases were of two types: central with memory disorders and temporal lobe seizures, or peripheral with muscular hyperactivity. Overall, we review the up-to-date knowledge on CASPR2 function and pinpoint confused or lacking information that will need further investigation., (© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)
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- 2018
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85. Comparisons in fluctuation of muscle strength and function in patients with immune-mediated neuropathy treated with intravenous versus subcutaneous immunoglobulin.
- Author
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Christiansen I, Markvardsen LH, and Jakobsen J
- Subjects
- Adult, Aged, Aged, 80 and over, Autoimmune Diseases of the Nervous System physiopathology, Autoimmune Diseases of the Nervous System therapy, Female, Hand Strength, Humans, Immunoglobulin G blood, Immunoglobulin G therapeutic use, Immunologic Factors therapeutic use, Injections, Subcutaneous, Male, Middle Aged, Peripheral Nervous System Diseases physiopathology, Peripheral Nervous System Diseases therapy, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating physiopathology, Prospective Studies, Walk Test, Immunoglobulin G administration & dosage, Immunoglobulins, Intravenous therapeutic use, Immunologic Factors administration & dosage, Muscle Strength, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating therapy
- Abstract
Introduction: Variations in muscle strength and function have not been studied in patients with chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy whose treatment regimen has been changed from intravenous to subcutaneous immunoglobulin (IVIg to SCIg)., Methods: In a prospective, open-label study, patients were changed from monthly IVIg to weekly SCIg. The primary endpoint was variation in isokinetic muscle strength (cIKS). Secondary endpoints were variations in Medical Research Council (MRC) score, grip strength (GS), 9-hole-peg test (9-HPT), and 40-meter-walk test (40-MWT)., Results: The coefficient of variance of cIKS during the IVIg and SCIg treatment periods was unchanged (mean ± SD: 6.97 ± 4.83% vs. 5.50 ± 3.13%, P = 0.21). The variations in the 9-HPT and 40-MWT were significantly lower in the SCIg group (P = 0.01 and P = 0.005, respectively)., Discussion: When therapy was changed from IVIg to SCIg, fluctuation of muscle strength was unchanged, but performance fluctuations were diminished. Muscle Nerve 57: 610-614, 2018., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2018
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86. Clinical and immunological characteristics of the spectrum of GFAP autoimmunity: a case series of 22 patients.
- Author
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Iorio R, Damato V, Evoli A, Gessi M, Gaudino S, Di Lazzaro V, Spagni G, Sluijs JA, and Hol EM
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Autoimmune Diseases of the Nervous System complications, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System therapy, Brain diagnostic imaging, Breast Neoplasms complications, Carcinoma complications, Cerebellar Ataxia complications, Cerebellar Ataxia immunology, Cerebellar Ataxia physiopathology, Cerebellar Ataxia therapy, Child, Drug Resistant Epilepsy complications, Drug Resistant Epilepsy immunology, Drug Resistant Epilepsy physiopathology, Drug Resistant Epilepsy therapy, Encephalomyelitis complications, Encephalomyelitis immunology, Encephalomyelitis physiopathology, Encephalomyelitis therapy, Female, Glial Fibrillary Acidic Protein genetics, Glucocorticoids therapeutic use, Humans, Immunoglobulins, Intravenous therapeutic use, Immunologic Factors therapeutic use, Immunotherapy, Magnetic Resonance Imaging, Male, Meningoencephalitis complications, Meningoencephalitis immunology, Meningoencephalitis physiopathology, Meningoencephalitis therapy, Mice, Mice, Knockout, Middle Aged, Movement Disorders complications, Movement Disorders immunology, Movement Disorders physiopathology, Movement Disorders therapy, Myelitis complications, Myelitis immunology, Myelitis physiopathology, Myelitis therapy, Myoclonus complications, Myoclonus immunology, Myoclonus physiopathology, Myoclonus therapy, Optic Neuritis complications, Optic Neuritis immunology, Optic Neuritis physiopathology, Optic Neuritis therapy, Ovarian Neoplasms complications, Plasma Exchange, Protein Isoforms, Spinal Cord diagnostic imaging, Thymoma complications, Thymus Neoplasms complications, Young Adult, Autoantibodies immunology, Autoimmune Diseases of the Nervous System physiopathology, Glial Fibrillary Acidic Protein immunology
- Abstract
Objective: To report the clinical and immunological characteristics of 22 new patients with glial fibrillar acidic protein (GFAP) autoantibodies., Methods: From January 2012 to March 2017, we recruited 451 patients with suspected neurological autoimmune disease at the Catholic University of Rome. Patients' serum and cerebrospinal fluid (CSF) samples were tested for neural autoantibodies by immunohistochemistry on mouse and rat brain sections, by cell-based assays (CBA) and immunoblot. GFAP autoantibodies were detected by immunohistochemistry and their specificity confirmed by CBA using cells expressing human GFAPα and GFAPδ proteins, by immunoblot and immunohistochemistry on GFAP-/- mouse brain sections., Results: Serum and/or CSF IgG of 22/451 (5%) patients bound to human GFAP, of which 22/22 bound to GFAPα, 14/22 to both GFAPα and GFAPδ and none to the GFAPδ isoform only. The neurological presentation was: meningoencephalomyelitis or encephalitis in 10, movement disorder (choreoathetosis or myoclonus) in 3, anti-epileptic drugs (AED)-resistant epilepsy in 3, cerebellar ataxia in 3, myelitis in 2, optic neuritis in 1 patient. Coexisting neural autoantibodies were detected in five patients. Six patients had other autoimmune diseases. Tumours were found in 3/22 patients (breast carcinoma, 1; ovarian carcinoma, 1; thymoma, 1). Nineteen patients were treated with immunotherapy and 16 patients (84%) improved. Histopathology analysis of the leptomeningeal biopsy specimen from one patient revealed a mononuclear infiltrate with macrophages and CD8+ T cells., Conclusions: GFAP autoimmunity is not rare. The clinical spectrum encompasses meningoencephalitis, myelitis, movement disorders, epilepsy and cerebellar ataxia. Coexisting neurological and systemic autoimmunity are relatively common. Immunotherapy is beneficial in most cases., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
- Published
- 2018
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87. Seronegative autoimmune autonomic neuropathy: a distinct clinical entity.
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Golden EP, Bryarly MA, and Vernino S
- Subjects
- Adult, Aged, Autoantibodies blood, Autoantigens immunology, Autoimmune Diseases of the Nervous System blood, Autonomic Nervous System Diseases physiopathology, Female, Humans, Male, Receptors, Cholinergic immunology, Retrospective Studies, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System physiopathology, Autonomic Nervous System Diseases immunology
- Abstract
Purpose: Autoimmune autonomic ganglionopathy (AAG) is associated with ganglionic acetylcholine receptor (gAChR) antibodies. We describe a similar but distinct series of patients with autoimmune autonomic failure lacking this antibody., Methods: Retrospective chart review., Results: Six patients presented with subacute autonomic failure, seronegative for gAChR antibodies. Orthostatic hypotension and gastrointestinal complaints were common. Autonomic testing revealed predominant sympathetic failure and no premature pupillary redilation. All patients had sensory symptoms and/or pain, which was severe in three. Immunotherapy with plasma exchange, intravenous immunoglobulin, and rituximab was ineffective. Three patients responded to intravenous steroids., Conclusion: In these cases of autoimmune autonomic failure, key differences from seropositive AAG emerge. Testing showed prominent sympathetic (rather than cholinergic) failure, specific pupillary findings of AAG were absent, and sensory symptoms were prominent. AAG responds to antibody-targeted immunotherapy, while these patients responded best to steroids. This seronegative autoimmune autonomic neuropathy is a distinct clinical entity requiring a different treatment approach from AAG.
- Published
- 2018
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88. Gangliosides and Autoimmune Peripheral Nerve Diseases.
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Goodfellow JA and Willison HJ
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- Animals, Humans, Autoimmune Diseases of the Nervous System physiopathology, Gangliosides metabolism, Peripheral Nervous System Diseases physiopathology
- Abstract
A wide range of neuroimmunological diseases, referred to as autoimmune neuropathies, affect the peripheral nervous systems (PNS). The PNS is structurally diverse with complex anatomical compartments enriched in many different myelin and neuronal glycolipids, notably gangliosides. Autoimmune neuropathies are a proportion of autoimmune neuropathies mediated by autoimmune attack due to antibodies reactive with these compartmentally localized gangliosides. Antiganglioside antibodies are principally associated with the acute paralytic disease, Guillain-Barré syndrome, and are also found in several chronic autoimmune neuropathy syndromes. These antibodies may arise spontaneously from the natural autoantibody repertoire, or be induced by infections that share structurally similar glycans to gangliosides, an immunological process often referred to as molecular mimicry. The principal infection exhibiting this structural similarity is Campylobacter jejuni, which displays mimics of GM1, GD1a, GT1a, and other gangliosides on its surface lipo-oligosaccharide. Autoantibodies thus induced bind glycan epitopes on peripheral nerve gangliosides where they activate complement and recruit macrophages, causing structural and functional disorganization of nerve conduction. Chronic autoimmune neuropathies are also associated with naturally arising IgM antibodies directed against ganglioside epitopes present on disialylated gangliosides, that induce a sensory neuropathy, and on GM1, that induce a motor neuropathy. In a third syndrome, the so-called "anti-MAG" neuropathy, the antibodies bind a sulfated glucuronic acid epitope present on myelin-associated glycoprotein and the glycolipid sulfated glucuronyl paragloboside. This review will describe the immunological, pathological, and clinical features of these disorders in the context of our broader knowledge of the ganglioside glycobiology of the peripheral nervous system., (Copyright © 2018. Published by Elsevier Inc.)
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- 2018
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89. Phenotypic and Molecular Spectrum of Aicardi-Goutières Syndrome: A Study of 24 Patients.
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Al Mutairi F, Alfadhel M, Nashabat M, El-Hattab AW, Ben-Omran T, Hertecant J, Eyaid W, Ali R, Alasmari A, Kara M, Al-Twaijri W, Filimban R, Alshenqiti A, Al-Owain M, Faqeih E, and Alkuraya FS
- Subjects
- Atrophy pathology, Child, Child, Preschool, Consanguinity, Female, Humans, Infant, Libya, Male, Qatar, Saudi Arabia, United Arab Emirates, Autoimmune Diseases of the Nervous System complications, Autoimmune Diseases of the Nervous System genetics, Autoimmune Diseases of the Nervous System pathology, Autoimmune Diseases of the Nervous System physiopathology, Epilepsy etiology, Epilepsy genetics, Epilepsy pathology, Epilepsy physiopathology, Muscle Spasticity etiology, Muscle Spasticity genetics, Muscle Spasticity pathology, Muscle Spasticity physiopathology, Nervous System Malformations complications, Nervous System Malformations genetics, Nervous System Malformations pathology, Nervous System Malformations physiopathology, Neurodevelopmental Disorders etiology, Neurodevelopmental Disorders genetics, Neurodevelopmental Disorders physiopathology, Ribonucleases genetics, Seizures etiology, Seizures genetics, Seizures pathology, Seizures physiopathology, White Matter pathology
- Abstract
Background: Aicardi-Goutières syndrome is a rare genetic neurological disorder with variable clinical manifestations. Molecular detection of specific mutations is required to confirm the diagnosis. The aim of this study was to review the clinical and molecular diagnostic findings in 24 individuals with Aicardi-Goutières syndrome who presented during childhood in an Arab population., Materials and Methods: We reviewed the records of 24 patients from six tertiary hospitals in different Arab countries. All included patients had a molecular diagnosis of Aicardi-Goutières syndrome., Results: Six individuals with Aicardi-Goutières syndrome (25%) had a neonatal presentation, whereas the remaining patients presented during the first year of life. Patients presented with developmental delay (24 cases, 100%); spasticity (24 cases, 100%); speech delay (23 cases, 95.8%); profound intellectual disability (21 cases, 87.5%); truncal hypotonia (21 cases, 87.5%); seizures (eighteen cases, 75%); and epileptic encephalopathy (15 cases, 62.5%). Neuroimaging showed white matter abnormalities (22 cases, 91.7%), cerebral atrophy (75%), and small, multifocal calcifications in the lentiform nuclei and deep cerebral white matter (54.2%). Homozygous mutations were identified in RNASEH2B (54.2%), RNASEH2A (20.8%), RNASEH2C (8.3%), SAMHD1 (8.3%), TREX1 (4.2%), and heterozygous mutations in IFIH1 (4.2%), with c.356A>G (p.Asp119Gly) in RNASEH2B being the most frequent mutation. Three novel mutations c.987delT and c.625 + 1G>A in SAMHD1 gene and c.961G>T in the IFIHI1 gene were identified., Conclusions: This is the largest molecularly confirmed Aicardi-Goutières syndrome cohort from Arabia. By presenting these clinical and molecular findings, we hope to raise awareness of Aicardi-Goutières syndrome and to demonstrate the importance of specialist referral and molecular diagnosis., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2018
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90. Clinical Problem Solving: A Tobacco Merchant Who Can't Spit.
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Benizri S, Agmon-Levin N, Kitrey ND, Carter D, Goshen E, and Sharabi Y
- Subjects
- Autoantibodies blood, Constipation diagnosis, Constipation etiology, Diagnosis, Differential, Dry Eye Syndromes diagnosis, Dry Eye Syndromes etiology, Erectile Dysfunction diagnosis, Erectile Dysfunction etiology, Ganglia, Autonomic immunology, Ganglia, Autonomic physiopathology, Glucocorticoids administration & dosage, Humans, Immunologic Factors administration & dosage, Male, Middle Aged, Synaptic Transmission drug effects, Autoimmune Diseases of the Nervous System diagnosis, Autoimmune Diseases of the Nervous System drug therapy, Autoimmune Diseases of the Nervous System physiopathology, Autonomic Nervous System Diseases diagnosis, Autonomic Nervous System Diseases drug therapy, Autonomic Nervous System Diseases physiopathology, Hypotension, Orthostatic diagnosis, Hypotension, Orthostatic etiology, Receptors, Nicotinic immunology, Rituximab administration & dosage, Xerostomia diagnosis, Xerostomia etiology
- Abstract
Background: A 47 year old man presented with a combination of dry mouth and lightheadedness while standing. His medical background was unremarkable except for cigarette smoking and hyperlipidemia. Sjögren's syndrome was ruled out, and he was referred for evaluation of orthostatic hypotension, which by then included syncopal episodes and injuries. Additional symptoms included dry eyes, constipation, reduced sweating, and erectile dysfunction. After excluding medications and structural cardiac abnormalities as causes of orthostatic hypotension, a clinical autonomic evaluation was performed. The pattern of beat-to-beat blood pressure associated with performance of the Valsalva maneuver, and a low plasma norepinephrine level that did not increase in response to standing, established that the orthostatic hypotension was neurogenic. Treatment with an alpha-adrenoceptor agonist and fludrocortisone yielded partial improvement. After systemic diseases involving autonomic failure were excluded, cardiac sympathetic neuroimaging was performed by 123I-metaliodobenzylguanidine (MIBG) scanning. The normal uptake seen in the heart indicated intact post ganglionic sympathetic innervation. There were no signs of central neurodegeneration or peripheral neuropathy. Because of symptoms and signs of both parasympathetic and sympathetic failure without denervation, an autonomic ganglionopathy was considered. A high titer of antibody to the neuronal nicotinic receptor, which mediates ganglionic neurotransmission, was obtained. The diagnosis of autoimmune autonomic ganglionopathy (AAG) was made, and the management strategy shifted to first lowering the antibody burden by plasma exchanges and then instituting chronic anti-autoimmune treatment with rituximab and a low dose of cortiosteroid. The patient showed remarkable improvement.
- Published
- 2017
91. Neonatal detection of Aicardi Goutières Syndrome by increased C26:0 lysophosphatidylcholine and interferon signature on newborn screening blood spots.
- Author
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Armangue T, Orsini JJ, Takanohashi A, Gavazzi F, Conant A, Ulrick N, Morrissey MA, Nahhas N, Helman G, Gordish-Dressman H, Orcesi S, Tonduti D, Stutterd C, van Haren K, Toro C, Iglesias AD, van der Knaap MS, Goldbach Mansky R, Moser AB, Jones RO, and Vanderver A
- Subjects
- Autoimmune Diseases of the Nervous System genetics, Autoimmune Diseases of the Nervous System physiopathology, Child, Preschool, Chromatography, High Pressure Liquid, Chromatography, Liquid, Dried Blood Spot Testing methods, Exodeoxyribonucleases genetics, Female, Humans, Infant, Infant, Newborn, Inflammation blood, Inflammation genetics, Interferons genetics, Male, Mutation, Nervous System Malformations genetics, Nervous System Malformations physiopathology, Phosphoproteins genetics, Retrospective Studies, Sensitivity and Specificity, Tandem Mass Spectrometry, Transcriptome immunology, Autoimmune Diseases of the Nervous System blood, Autoimmune Diseases of the Nervous System diagnosis, Interferons blood, Lysophosphatidylcholines blood, Neonatal Screening methods, Nervous System Malformations blood, Nervous System Malformations diagnosis
- Abstract
Background: Aicardi Goutières Syndrome (AGS) is a heritable interferonopathy associated with systemic autoinflammation causing interferon (IFN) elevation, central nervous system calcifications, leukodystrophy and severe neurologic sequelae. An infant with TREX1 mutations was recently found to have abnormal C26:0 lysophosphatidylcholine (C26:0 Lyso-PC) in a newborn screening platform for X-linked adrenoleukodystrophy, prompting analysis of this analyte in retrospectively collected samples from individuals affected by AGS., Methods: In this study, we explored C26:0 Lyso-PC levels and IFN signatures in newborn blood spots and post-natal blood samples in 19 children with a molecular and clinical diagnosis of AGS and in the blood spots of 22 healthy newborns. We used Nanostring nCounter™ for IFN-induced gene analysis and a high-performance liquid chromatography with tandem mass spectrometry (HPLC MS/MS) newborn screening platform for C26:0 Lyso-PC analysis., Results: Newborn screening cards from patients across six AGS associated genes were collected, with a median disease presentation of 2months. Thirteen out of 19 (68%) children with AGS had elevations of first tier C26:0 Lyso-PC (>0.4μM), that would have resulted in a second screen being performed in a two tier screening system for X-linked adrenoleukodystrophy (X-ALD). The median (95%CI) of first tier C26:0 Lyso-PC values in AGS individuals (0.43μM [0.37-0.48]) was higher than that seen in controls (0.21μM [0.21-0.21]), but lower than X-ALD individuals (0.72μM [0.59-0.84])(p<0.001). Fourteen of 19 children had elevated expression of IFN signaling on blood cards relative to controls (Sensitivity 73.7%, 95%CI 51-88%, Specificity 95%, 95% CI 78-99%) including an individual with delayed disease presentation (36months of age). All five AGS patients with negative IFN signature at birth had RNASEH2B mutations. Consistency of agreement between IFN signature in neonatal and post-natal samples was high (0.85)., Conclusion: This suggests that inflammatory markers in AGS can be identified in the newborn period, before symptom onset. Additionally, since C26:0 Lyso-PC screening is currently used in X-ALD newborn screening panels, clinicians should be alert to the fact that AGS infants may present as false positives during X-ALD screening., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
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92. Roles of SAMHD1 in antiviral defense, autoimmunity and cancer.
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Li M, Zhang D, Zhu M, Shen Y, Wei W, Ying S, Korner H, and Li J
- Subjects
- Animals, Disease Models, Animal, Humans, Mice, Knockout, SAM Domain and HD Domain-Containing Protein 1 chemistry, SAM Domain and HD Domain-Containing Protein 1 genetics, Antiviral Agents metabolism, Autoimmune Diseases of the Nervous System physiopathology, Neoplasms physiopathology, Nervous System Malformations physiopathology, SAM Domain and HD Domain-Containing Protein 1 metabolism, Virus Diseases immunology
- Abstract
The enzyme, sterile α motif and histidine-aspartic acid domain-containing protein 1 (SAMHD1) diminishes infection of human immunodeficiency virus type 1 (HIV-1) by hydrolyzing intracellular deoxynucleotide triphosphates (dNTPs) in myeloid cells and resting CD4+ T cells. This dNTP degradation reduces the dNTP concentration to a level insufficient for viral cDNA synthesis, thereby inhibiting retroviral replication. This antiviral enzymatic activity can be inhibited by viral protein X (Vpx). The HIV-2/SIV Vpx causes degradation of SAMHD1, thus interfering with the SAMHD1-mediated restriction of retroviral replication. Recently, SAMHD1 has been suggested to restrict HIV-1 infection by directly digesting genomic HIV-1 RNA through a still controversial RNase activity. Here, we summarize the current knowledge about structure, antiviral mechanisms, intracellular localization, interferon-regulated expression of SAMHD1. We also describe SAMHD1-deficient animal models and an antiviral drug on the basis of disrupting proteasomal degradation of SAMHD1. In addition, the possible roles of SAMHD1 in regulating innate immune sensing, Aicardi-Goutières syndrome and cancer are discussed in this review., (Copyright © 2017 John Wiley & Sons, Ltd.)
- Published
- 2017
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93. The value of LGI1, Caspr2 and voltage-gated potassium channel antibodies in encephalitis.
- Author
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van Sonderen A, Petit-Pedrol M, Dalmau J, and Titulaer MJ
- Subjects
- Animals, Autoimmune Diseases of the Nervous System diagnosis, Autoimmune Diseases of the Nervous System physiopathology, Encephalitis diagnosis, Encephalitis physiopathology, Humans, Intracellular Signaling Peptides and Proteins, Potassium Channels, Voltage-Gated agonists, Autoantibodies immunology, Autoimmune Diseases of the Nervous System immunology, Encephalitis immunology, Membrane Proteins immunology, Nerve Tissue Proteins immunology, Potassium Channels, Voltage-Gated immunology, Proteins immunology
- Abstract
The discovery, in 2010, of autoantibodies against the extracellular proteins LGI1 and Caspr2 facilitated a change of view regarding the clinical importance of voltage-gated potassium channel (VGKC) antibodies. Currently, these antibodies are all classified as VGKC-complex antibodies, and are commonly considered to have a similar clinical value. However, studies from the past few years show that the immune responses mediated by these antibodies have differing clinical relevance. Here, we review the clinical importance of these immune responses in three settings: patients with anti-LGI1 antibodies, patients with anti-Caspr2 antibodies, and patients with antibodies against the VGKC complex that lack LGI1 and Caspr2 specificity. Antibodies against LGI1 and Caspr2 are associated with different but well-defined syndromes, whereas the clinical importance of VGKC-complex antibodies without LGI1 and Caspr2 specificity is questionable. We describe each of these syndromes, discuss the function of the target antigens and review the limited paediatric literature on the topic. The findings emphasize the importance of defining these disorders according to the molecular identity of the targets (LGI1 or Caspr2), and caution against the use of VGKC-complex antibodies for the diagnosis and treatment of patients without further definition of the antigen.
- Published
- 2017
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94. Brown-Vialetto-Van Laere Syndrome as a Mimic of Neuroimmune Disorders: 3 Cases From the Clinic and Review of the Literature.
- Author
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Allison T, Roncero I, Forsyth R, Coffman K, and Pichon JL
- Subjects
- Adolescent, Bulbar Palsy, Progressive genetics, Child, Preschool, Disease Progression, Female, Hearing Loss, Sensorineural genetics, Humans, Membrane Transport Proteins genetics, Mutation genetics, Autoimmune Diseases of the Nervous System physiopathology, Bulbar Palsy, Progressive diagnosis, Hearing Loss, Sensorineural diagnosis
- Abstract
We present 3 patients identified at 2 different institutions with Brown-Vialetto-Van Laere syndrome. Each patient was initially diagnosed with a neuroimmune disorder for a period of a few weeks to a few months. In each case, genetic analysis revealed mutations in one of the riboflavin transporters, confirming Brown-Vialetto-Van Laere syndrome. It is likely that Brown-Vialetto-Van Laere syndrome is more common than previously reported, and because it mimics neuroimmune disorders, it may be misdiagnosed as such. It shares many features with diseases such as chronic inflammatory demyelinating neuropathy, may present with positive cerebrospinal fluid antibody titers, and may transiently respond to intravenous immunoglobulin. We review the literature on Brown-Vialetto-Van Laere syndrome and Fazio-Londe syndrome, 2 riboflavin transporter disorders, looking for clinical presentations that may lead to confusion with neuroimmune disorders. We emphasize the importance of correctly diagnosing the disease, as its treatment is relatively benign and will stop progression of the disease and may even reverse it.
- Published
- 2017
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95. The Blood-Brain Barrier: Regulatory Roles in Wakefulness and Sleep.
- Author
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Pan W and Kastin AJ
- Subjects
- Animals, Autoimmune Diseases of the Nervous System metabolism, Blood-Brain Barrier metabolism, Humans, Neurodegenerative Diseases metabolism, Sleep Deprivation metabolism, Autoimmune Diseases of the Nervous System physiopathology, Biological Transport physiology, Blood-Brain Barrier physiology, Circadian Rhythm physiology, Neurodegenerative Diseases physiopathology, Sleep physiology, Sleep Deprivation physiopathology, Wakefulness physiology
- Abstract
Sleep and its disorders are known to affect the functions of essential organs and systems in the body. However, very little is known about how the blood-brain barrier (BBB) is regulated. A few years ago, we launched a project to determine the impact of sleep fragmentation and chronic sleep restriction on BBB functions, including permeability to fluorescent tracers, tight junction protein expression and distribution, glucose and other solute transporter activities, and mediation of cellular mechanisms. Recent publications and relevant literature allow us to summarize here the sleep-BBB interactions in five sections: (1) the structural basis enabling the BBB to serve as a huge regulatory interface; (2) BBB transport and permeation of substances participating in sleep-wake regulation; (3) the circadian rhythm of BBB function; (4) the effect of experimental sleep disruption maneuvers on BBB activities, including regional heterogeneity, possible threshold effect, and reversibility; and (5) implications of sleep disruption-induced BBB dysfunction in neurodegeneration and CNS autoimmune diseases. After reading the review, the general audience should be convinced that the BBB is an important mediating interface for sleep-wake regulation and a crucial relay station of mind-body crosstalk. The pharmaceutical industry should take into consideration that sleep disruption alters the pharmacokinetics of BBB permeation and CNS drug delivery, being attentive to the chrono timing and activation of co-transporters in subjects with sleep disorders.
- Published
- 2017
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96. A comprehensive analysis and immunobiology of autoimmune neurological syndromes during the Zika virus outbreak in Cúcuta, Colombia.
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Anaya JM, Rodríguez Y, Monsalve DM, Vega D, Ojeda E, González-Bravo D, Rodríguez-Jiménez M, Pinto-Díaz CA, Chaparro P, Gunturiz ML, Ansari AA, Gershwin ME, Molano-González N, Ramírez-Santana C, and Acosta-Ampudia Y
- Subjects
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Autoimmune Diseases of the Nervous System diagnosis, Autoimmune Diseases of the Nervous System epidemiology, Case-Control Studies, Child, Child, Preschool, Cluster Analysis, Colombia epidemiology, Disease Outbreaks, Female, Geography, Medical, Guillain-Barre Syndrome diagnosis, Guillain-Barre Syndrome epidemiology, Guillain-Barre Syndrome etiology, Guillain-Barre Syndrome physiopathology, Humans, Infant, Male, Middle Aged, Odds Ratio, Pregnancy, Public Health Surveillance, Sex Factors, Symptom Assessment, Young Adult, Zika Virus Infection epidemiology, Zika Virus Infection transmission, Autoimmune Diseases of the Nervous System etiology, Autoimmune Diseases of the Nervous System physiopathology, Zika Virus immunology, Zika Virus Infection complications, Zika Virus Infection immunology
- Abstract
We have focused on the epidemiology and immunobiology of Zika virus (ZIKV) infection and factors associated with the development of Guillain-Barré syndrome (GBS) and other neurological syndromes in Cúcuta, the capital of North Santander department, Colombia. Data of patients with ZIKV disease reported to the national population-based surveillance system were used to calculate the basic reproduction number (R
0 ) and the attack rates (ARs) as well as to develop epidemiological maps. Patients with neurological syndromes were contacted and their diagnoses were confirmed. A case-control study in which 29 patients with GBS associated with ZIKV compared with 74-matched control patients with ZIKV infection alone was undertaken. Antibodies against arboviruses and other infections that may trigger GBS were evaluated. The estimated value of R0 ranged between 2.68 (95% CI 2.54-2.67) to 4.57 (95% CI 4.18-5.01). The sex-specific ARs were 1306 per 100,000 females, and 552 per 100,000 males. A non-linear interaction between age and gender on the ARs was observed. The incidence of GBS in Cúcuta increased 4.41 times secondary to ZIKV infection. The lag time between ZIKV infection and neurological symptoms was 7 days (interquartile range 2-14.5). Patients with GBS appeared to represent a lower socioeconomic status and were living near to environmentally contaminated areas. All GBS patients were positive for IgG antibodies against both ZIKV and Dengue virus, and 69% were positive for Chikungunya virus. Noteworthy, GBS was associated with a previous infection with M. pneumoniae (OR: 3.95; 95% CI 1.44-13.01; p = 0.006). No differences in antibody levels against C. jejuni, Epstein-Barr virus and cytomegalovirus were observed. High rates of cranial nerves involvement and dysautonomia were present in 82% and 75.9%, respectively. Intensive care unit (ICU) admission was necessary in 69% of the GBS patients. Most of the patients disclosed a high disability condition (Hughes grade 4). Dysautonomia was the main risk factor of poor GBS prognosis (i.e., ICU admission and disability). Thirteen patients were diagnosed with other neurological syndromes different to GBS (6 with transverse myelitis, 3 with encephalitis, 3 with peripheral facial palsy and one with thoraco-lumbosacral myelopathy). Our data confirm an increased transmission of ZIKV in Cúcuta, and provide support to the view that severe neurological syndromes are related to ZIKV disease. The complex ways by which previous infections and socioeconomic status interact to increase the risk of GBS in people infected by ZIKV should be further investigated., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2017
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97. Autoimmune Encephalitides: A Broadening Field of Treatable Conditions.
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Kalman B
- Subjects
- Autoimmune Diseases of the Nervous System epidemiology, Autoimmune Diseases of the Nervous System physiopathology, Encephalitis epidemiology, Encephalitis physiopathology, Humans, Paraneoplastic Syndromes, Nervous System epidemiology, Paraneoplastic Syndromes, Nervous System physiopathology, Autoimmune Diseases of the Nervous System immunology, Encephalitis immunology, Paraneoplastic Syndromes, Nervous System immunology
- Abstract
Background: Neurology has been continuously transforming by the refinement of molecular diagnostics and the development of disease-modifying treatments. The discovery of new antibody markers has elucidated the pathogenesis, provided the means of diagnostics, and offered cure or treatment for several immune-mediated neurological and neuropsychiatric disorders. The identification of pathogenic and marker autoantibodies has also facilitated defining the associated phenotypic spectra and the overlap among the phenotypes linked to individual immune markers., Review Summary: This survey presents the list of currently known autoimmune encephalitis entities along with the associated marker autoantibodies, highlights the phenotypic and immune pathogenic relationships, calls attention to the recently described rare syndromes, discusses the biological significance of the autoantibodies and targeted molecules, points out the potential postinfectious origin of immune pathogenesis in several of the disorders, and directs the readers to the latest diagnostic guidelines as well as to the generally used treatment approaches., Conclusions and Future Directions: Owing to the successful and usually combined use of various methods to detect serum and cerebrospinal fluid autoantibodies on rodent brain sections, in primary neuronal cell culture, in immune precipitation, and cell-based assays, or in other antigen-specific immune assays (Western blot, enzyme-linked immunosorbent assay, and radioimmune assay), the subgroup of antibody marker-negative autoimmune encephalopathy syndromes is contracting, whereas the numbers of entities within the overall group are expanding. Recognition of the correct diagnosis is becoming increasingly rewarding not only for neurologists, but also for pediatric neurologists and psychiatrists.
- Published
- 2017
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98. An orphan disease: IgG4-related spinal pachymeningitis: report of 2 cases.
- Author
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Radotra BD, Aggarwal A, Kapoor A, Singla N, and Chatterjee D
- Subjects
- Diagnosis, Differential, Humans, Male, Middle Aged, Radiculopathy diagnostic imaging, Radiculopathy pathology, Radiculopathy physiopathology, Radiculopathy therapy, Spinal Cord Diseases diagnostic imaging, Spinal Cord Diseases pathology, Spinal Cord Diseases physiopathology, Young Adult, Autoimmune Diseases of the Nervous System diagnostic imaging, Autoimmune Diseases of the Nervous System pathology, Autoimmune Diseases of the Nervous System physiopathology, Autoimmune Diseases of the Nervous System therapy, Immunoglobulin G, Meningitis diagnostic imaging, Meningitis pathology, Meningitis physiopathology, Meningitis therapy, Rare Diseases diagnostic imaging, Rare Diseases pathology, Rare Diseases physiopathology, Rare Diseases therapy, Spinal Cord Diseases therapy
- Abstract
IgG4-related disease is relatively new disease entity and a rare one, and our knowledge of this entity continues to evolve. It was first described in the pancreas and since then has been described in virtually every organ. Spinal involvement resulting in pachymeningitis is rare, and there are only 8 reported cases of the same to date, with the cervicothoracic spine being the most commonly affected region. The authors describe 2 cases in which the patients presented with spinal compression resulting in myeloradiculopathy (Case 1) and radiculopathy (Case 2). Imaging of spine in both cases revealed an ill-defined contrast-enhancing lesion at the lumbar level. Preoperatively, a diagnosis of spinal tumor was made, but intraoperatively no spinal tumor was found. The diagnosis was established histopathologically. The disease has no particular defining features clinically or radiologically and can mimic common spinal tumors. It is important to accurately diagnose this rare entity because of its multisystem involvement and progressive course. Strict treatment guidelines have yet to be formulated. Although histologically this disease can mimic other inflammatory conditions, the presence of storiform fibrosis and an increased number of IgG4-positive plasma cells can help in clarifying the diagnosis.
- Published
- 2016
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99. Nerve ultrasound protocol in differentiating chronic immune-mediated neuropathies.
- Author
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Kerasnoudis A, Pitarokoili K, Haghikia A, Gold R, and Yoon MS
- Subjects
- Adult, Aged, Autoimmune Diseases of the Nervous System classification, Autoimmune Diseases of the Nervous System physiopathology, Diagnosis, Differential, Electrophysiology, Female, Humans, Male, Middle Aged, Peripheral Nerves physiopathology, Sensitivity and Specificity, Autoimmune Diseases of the Nervous System diagnostic imaging, Peripheral Nerves diagnostic imaging, Ultrasonography
- Abstract
Introduction: In this study we evaluated a new neuropathy ultrasound protocol (NUP) for differentiating chronic immune-mediated neuropathies., Methods: The NUP was evaluated in 110 patients with clinical presentations of chronic immune-mediated neuropathy. All patients were first evaluated clinically and electrophysiologically and divided into 4 polyneuropathy groups: (a) symmetric demyelinating; (b) symmetric axonal; (c) asymmetric demyelinating; and (d) asymmetric axonal. During step 2, the NUP was evaluated prospectively for all 4 study groups., Results: Overall, the NUP led to correct classification in 42 of 49 (85.7%) patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 13 of 15 (86.9%) with multifocal motor neuropathy (MMN), and 5 of 5 (100%) with multifocal-acquired demyelinating sensory and motor neuropathy (MADSAM). The NUP had >80% sensitivity and specificity in distinguishing CIDP, MMN, and MADSAM in all 4 study groups., Conclusions: The NUP is a useful addition in the differential diagnosis of chronic immune-mediated neuropathies in everyday practice. Muscle Nerve 54: 864-871, 2016., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2016
- Full Text
- View/download PDF
100. Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy: A Novel Meningoencephalomyelitis.
- Author
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Fang B, McKeon A, Hinson SR, Kryzer TJ, Pittock SJ, Aksamit AJ, and Lennon VA
- Subjects
- Adult, Aged, Autoantibodies cerebrospinal fluid, Autoimmune Diseases of the Nervous System cerebrospinal fluid, Biomarkers blood, Biomarkers cerebrospinal fluid, Female, HEK293 Cells, Humans, Immunoglobulin G, Male, Meningoencephalitis cerebrospinal fluid, Middle Aged, Myelitis cerebrospinal fluid, Paraneoplastic Syndromes, Nervous System cerebrospinal fluid, Recurrence, Retrospective Studies, Young Adult, Astrocytes immunology, Autoantibodies blood, Autoimmune Diseases of the Nervous System blood, Autoimmune Diseases of the Nervous System physiopathology, Glial Fibrillary Acidic Protein immunology, Meningoencephalitis blood, Meningoencephalitis physiopathology, Myelitis blood, Myelitis physiopathology, Paraneoplastic Syndromes, Nervous System blood, Paraneoplastic Syndromes, Nervous System physiopathology
- Abstract
Importance: A novel astrocytic autoantibody has been identified as a biomarker of a relapsing autoimmune meningoencephalomyelitis that is immunotherapy responsive. Seropositivity distinguishes autoimmune glial fibrillary acidic protein (GFAP) meningoencephalomyelitis from disorders commonly considered in the differential diagnosis., Objective: To describe a novel IgG autoantibody found in serum or cerebrospinal fluid that is specific for a cytosolic intermediate filament protein of astrocytes., Design, Setting, and Participants: Retrospective review of the medical records of seropositive patients identified in the Mayo Clinic Neuroimmunology Laboratory from October 15, 1998, to April 1, 2016, in blinded comprehensive serologic evaluation for autoantibody profiles to aid the diagnosis of neurologic autoimmunity (and predict cancer likelihood)., Main Outcomes and Measures: Frequency and definition of novel autoantibody, the autoantigen's immunochemical identification, clinical and magnetic resonance imaging correlations of the autoantibody, and immunotherapy responsiveness., Results: Of 103 patients whose medical records were available for review, the 16 initial patients identified as seropositive were the subject of this study. Median age at neurologic symptom onset was 42 years (range, 21-73 years); there was no sex predominance. The novel neural autoantibody, which we discovered to be GFAP-specific, is disease spectrum restricted but not rare (frequency equivalent to Purkinje cell antibody type 1 [anti-Yo]). Its filamentous pial, subventricular, and perivascular immunostaining pattern on mouse tissue resembles the characteristic magnetic resonance imaging findings of linear perivascular enhancement in patients. Prominent clinical manifestations are headache, subacute encephalopathy, optic papillitis, inflammatory myelitis, postural tremor, and cerebellar ataxia. Cerebrospinal fluid was inflammatory in 13 of 14 patients (93%) with data available. Neoplasia was diagnosed within 3 years of neurologic onset in 6 of 16 patients (38%): prostate and gastroesophageal adenocarcinomas, myeloma, melanoma, colonic carcinoid, parotid pleomorphic adenoma, and teratoma. Neurologic improvement followed treatment with high-dose corticosteroids, with a tendency of patients to relapse without long-term immunosuppression., Conclusions and Relevance: Glial fibrillary acidic protein-specific IgG identifies a distinctive, corticosteroid-responsive, sometimes paraneoplastic autoimmune meningoencephalomyelitis. It has a lethal canine equivalent: necrotizing meningoencephalitis. Expression of GFAP has been reported in some of the tumor types identified in paraneoplastic cases. Glial fibrillary acidic protein peptide-specific cytotoxic CD8+ T cells are implicated as effectors in a transgenic mouse model of autoimmune GFAP meningoencephalitis.
- Published
- 2016
- Full Text
- View/download PDF
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