Autoimmune episodic ataxia in patients with anti-CASPR2 antibody-associated encephalitis

Joubert, Bastien; Gobert, Florent; Thomas, Laure; Saint‐Martin, Margaux; Desestret, Virginie; Convers, Philippe; Rogemond, Véronique; Picard, Géraldine; Ducray, François; Psimaras, Dimitri; Antoine, Jean‐Christophe; Delattre, Jean‐Yves; Honnorat, Jérôme

doi:10.1212/nxi.0000000000000371

Cited by 81 publications

(45 citation statements)

References 17 publications

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“… Neurological autoimmune disease Gene variant Alteration-Mechanism Reference Autoimmune ataxia CACNA1A Mutation in intron 39 (c5843-14G>A) play an essential role in calcium channels. [ 227 ] ITPR1 c.7721T>C(p.V2574A) Alteration in IP3 signaling by disrupting the calcium influx. [ 228 ] Autoimmune epilepsy LGI1 Modulation of Voltage-Gated Potassium Channel activity.…”

Section: Genetic Factorsmentioning

confidence: 99%

Identifying the culprits in neurological autoimmune diseases

Acosta-Ampudia

Monsalve

Ramírez-Santana

2019

Journal of Translational Autoimmunity

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The target organ of neurological autoimmune diseases (NADs) is the central or peripheral nervous system. Multiple sclerosis (MS) is the most common NAD, whereas Guillain-Barré syndrome (GBS), myasthenia gravis (MG), and neuromyelitis optica (NMO) are less common NADs, but the incidence of these diseases has increased exponentially in the last few years. The identification of a specific culprit in NADs is challenging since a myriad of triggering factors interplay with each other to cause an autoimmune response. Among the factors that have been associated with NADs are genetic susceptibility, epigenetic mechanisms, and environmental factors such as infection, microbiota, vitamins, etc. This review focuses on the most studied culprits as well as the mechanisms used by these to trigger NADs.

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Section: Genetic Factorsmentioning

confidence: 99%

Identifying the culprits in neurological autoimmune diseases

Acosta-Ampudia

Monsalve

Ramírez-Santana

2019

Journal of Translational Autoimmunity

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“…Interestingly, a 64-year-old anti-Caspr2 Ab-positive man with paroxysmal episodes of CAs was reported [ 120 ]. He developed a paroxysmal episode of CAs one month after anti-Caspr2 Ab encephalitis.…”

Section: Clinical Autoimmune Background and Pathophysiological Actmentioning

confidence: 99%

“…He developed a paroxysmal episode of CAs one month after anti-Caspr2 Ab encephalitis. The authors retrospectively identified stereotyped episodes of paroxysmal CAs in five among 37 patients with anti-Caspr2 Ab-associated diseases [ 120 ]. The ataxic episodes, including gait imbalance (five patients), limb ataxia (three patients), slurred speech (three patients), and nystagmus (one patient), lasted a few minutes to a few days, and usually improved following immunotherapy (four patients), and sometimes spontaneously (one patient).…”

Section: Clinical Autoimmune Background and Pathophysiological Actmentioning

confidence: 99%

Fundamental Mechanisms of Autoantibody-Induced Impairments on Ion Channels and Synapses in Immune-Mediated Cerebellar Ataxias

Mitoma

Honnorat

Yamaguchi

et al. 2020

IJMS

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In the last years, different kinds of limbic encephalitis associated with autoantibodies against ion channels and synaptic receptors have been described. Many studies have demonstrated that such autoantibodies induce channel or receptor dysfunction. The same mechanism is discussed in immune-mediated cerebellar ataxias (IMCAs), but the pathogenesis has been less investigated. The aim of the present review is to evaluate what kind of cerebellar ion channels, their related proteins, and the synaptic machinery proteins that are preferably impaired by autoantibodies so as to develop cerebellar ataxias (CAs). The cerebellum predictively coordinates motor and cognitive functions through a continuous update of an internal model. These controls are relayed by cerebellum-specific functions such as precise neuronal discharges with potassium channels, synaptic plasticity through calcium signaling pathways coupled with voltage-gated calcium channels (VGCC) and metabotropic glutamate receptors 1 (mGluR1), a synaptic organization with glutamate receptor delta (GluRδ), and output signal formation through chained GABAergic neurons. Consistently, the association of CAs with anti-potassium channel-related proteins, anti-VGCC, anti-mGluR1, and GluRδ, and anti-glutamate decarboxylase 65 antibodies is observed in IMCAs. Despite ample distributions of AMPA and GABA receptors, however, CAs are rare in conditions with autoantibodies against these receptors. Notably, when the autoantibodies impair synaptic transmission, the autoimmune targets are commonly classified into three categories: release machinery proteins, synaptic adhesion molecules, and receptors. This physiopathological categorization impacts on both our understanding of the pathophysiology and clinical prognosis.

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“…37 These antibodies can cause a broad range of neurological syndromes and are found in association with malignancy in approximately one-third of cases. CASPR2-associated ataxia can present as an episodic disorder, with initially reported attacks triggered by postural changes and/or emotions 38 both CASPR2 and GFAP antibody-positive patients respond to immunotherapy when caught early. Finally, NMDAR antibodies have also been described rarely with ataxia without other classic NMDAR encephalitis features.…”

Section: Cerebellar Ataxiamentioning

confidence: 99%

Autoimmune Movement Disorders

Fearon

O’Toole

2018

Semin Neurol

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Autoimmune movement disorders are rare but potentially treatable entities. They can present with an excess or paucity of movement and may have other associated neurological symptoms. These disorders were originally recognized by their classic clinical presentations and the cancers associated with them. Recent emphasis has been targeted on associated, and sometimes causative, antibodies. Although some disorders have stereotypical presentations, the spectrum of abnormalities reported in association with antibodies is widening. Determining whether antibodies are incidental or pathogenic and, hence, foregoing or commencing immunotherapy treatment can be challenging for practicing neurologists. Physicians often have to make the decision to empirically treat patients while awaiting test results. Due to the lack of randomized controlled trials, the ideal immunotherapy treatments and regimens are unknown. Patients with intracellularly targeted antibodies tend to fare less well, while those with extracellularly targeted antibody disorders often respond to treatments reducing antibody production. This review aims to summarize reported adult-onset autoimmune movement disorders to date, and to provide a template for the workup and treatment of suspected disorders. Rarer antibodies that are not yet fully characterized, or reported in a few cases only, will not be covered in detail as these are not likely to be readily commercially available. Childhood disorders will be only be mentioned briefly in the discussion, as there is a separate article in this issue on autoimmune neurologic diseases in children.

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Autoimmune episodic ataxia in patients with anti-CASPR2 antibody-associated encephalitis

Cited by 81 publications

References 17 publications

Identifying the culprits in neurological autoimmune diseases

Identifying the culprits in neurological autoimmune diseases

Fundamental Mechanisms of Autoantibody-Induced Impairments on Ion Channels and Synapses in Immune-Mediated Cerebellar Ataxias

Autoimmune Movement Disorders

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