Fulminant Anti-GAD antibody encephalitis presenting with status epilepticus requiring aggressive immunosuppression

Triplett, James; Vijayan, Srimathy; MacDonald, Allycia; Lawn, Nicholas; McLean‐Tooke, Andrew; Bynevelt, Michael; Phatouros, Constantine C.; Chemmanam, Thomas

doi:10.1016/j.jneuroim.2018.06.013

Cited by 26 publications

(13 citation statements)

References 28 publications

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“…Anti-GAD antibodies are seen in patients with pharmacoresistant epilepsy, most often temporal lobe epilepsy [67][68][69]. Some patients present with refractory convulsive and non-convulsive status epilepticus with frequent autoimmune comorbidities but normal MRI [70][71][72][73][74], In a retrospective series, anti-GAD antibodies were detected in 22% of patients with various epilepsies and concurrent autoimmune comorbidities [72]. Among 233 patients with all types of GABAergic interneuron is impaired as in SPS, the a-motor neuron is continuously firing and the muscle will be continuously stimulated becoming hypertonic (spastic), without the ability to relax, due to simultaneous contraction of both, the agonist and the antagonist muscles, as highlighted by two asterisks ** [modified from [9]] epilepsy, 2,3% had GAD-abs but, if only patients with focal epilepsy are considered, GAD-Abs were present in 16% of all cases [75].…”

Section: Gad-positive Autoimmune Epilepsymentioning

confidence: 99%

Stiff-person Syndrome and GAD Antibody-spectrum Disorders: GABAergic Neuronal Excitability, Immunopathogenesis and Update on Antibody Therapies

Dalakas

2022

Neurotherapeutics

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Although antibodies against Glutamic Acid Decarboxylase (GAD) were originally associated with Stiff Person Syndrome (SPS), they now denote the “GAD antibody-spectrum disorders (GAD-SD)” that include Cerebellar Ataxia, Autoimmune Epilepsy, Limbic Encephalitis, PERM and eye movement disorder. In spite of the unique clinical phenotype that each of these disorders has, there is significant overlapping symptomatology characterized by autoimmune neuronal excitability. In addition to GAD, three other autoantibodies, against glycine receptors, amphiphysin and gephyrin, are less frequently or rarely associated with SPS-SD. Very high serum anti-GAD antibody titers are a key diagnostic feature for all GAD-SD, commonly associated with the presence of GAD antibodies in the CSF, a reduced CSF GABA level and increased anti-GAD-specific IgG intrathecal synthesis denoting stimulation of B-cell clones in the CNS. Because anti-GAD antibodies from the various hyperexcitability syndromes recognize the same dominant GAD epitope, the clinical heterogeneity among GAD-SD patients remains unexplained. The paper highlights the biologic basis of autoimmune hyperexcitability connected with the phenomenon of reciprocal inhibition as the fundamental mechanism of the patients’ muscle stiffness and spasms; addresses the importance of high-GAD antibody titers in diagnosis, pinpointing the diagnostic challenges in patients with low-GAD titers or their distinction from functional disorders; and discusses whether high GAD-antibodies are disease markers or pathogenic in the context of their association with reduced GABA level in the brain and CSF. Finally, it focuses on therapies providing details on symptomatic GABA-enhancing drugs and the currently available immunotherapies in a step-by-step approach. The prospects of future immunotherapeutic options with antibody therapies are also summarized.

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Section: Gad-positive Autoimmune Epilepsymentioning

confidence: 99%

Stiff-person Syndrome and GAD Antibody-spectrum Disorders: GABAergic Neuronal Excitability, Immunopathogenesis and Update on Antibody Therapies

Dalakas

2022

Neurotherapeutics

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“…However, a literature search shows reports of patients presenting with intractable seizures without a prodrome. 2,[10][11][12] In pediatric studies, patients were found to be between 2 and 17 years old, tended to be females and not have any associated underlying malignancy. 2,13,14 CSF analysis may be unremarkable, show oligoclonal bands, or pleocytosis.…”

Section: Discussionmentioning

confidence: 99%

Thalamic Lesions in a Toddler with Glutamic Acid Decarboxylase Autoimmune Encephalitis

Almuslamani

Taha

2020

Journal of Pediatric Neurology

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We present a child with glutamic acid decarboxylase (GAD) autoimmune encephalitis (AE) with bilateral thalamic lesions on magnetic resonance imaging (MRI) of the brain. A healthy 21-month-old girl, after superrefractory status epilepticus (SE) and fever developed dyskinesia and ataxia, which we subsequently diagnosed as GAD AE. She showed remarkable response to treatment with methylprednisolone and intravenous immunoglobulin (IVIg). Following an initial normal MRI of her brain, a further brain imaging showed bilateral thalamic lesions. This is a usual finding since brain imaging abnormalities, when found in GAD AE, mostly involve the mesial temporal lobe structures. Thalamic lesions in GAD AE have not been reported previously.

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“…Similar to other types of LE, GAD-associated LE is characterized by the subacute onset of seizures (53%) [93], anterograde amnesia (67%), and confusion and behavioral changes (30%) [93,114]. While virtually all patients will experience seizures at some point [93], status epilepticus is rarely reported [115,116]. Almost all patients experience cognitive impairment on the long term, with an impairment of memory and frontal lobe function [93].…”

Section: Limbic Encephalitis and Autoimmune Epilepsymentioning

confidence: 99%

Neurological Syndromes Associated with Anti-GAD Antibodies

Dade

Berzero

Izquierdo

et al. 2020

IJMS

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Glutamic acid decarboxylase (GAD) is an intracellular enzyme whose physiologic function is the decarboxylation of glutamate to gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter within the central nervous system. GAD antibodies (Ab) have been associated with multiple neurological syndromes, including stiff-person syndrome, cerebellar ataxia, and limbic encephalitis, which are all considered to result from reduced GABAergic transmission. The pathogenic role of GAD Ab is still debated, and some evidence suggests that GAD autoimmunity might primarily be cell-mediated. Diagnosis relies on the detection of high titers of GAD Ab in serum and/or in the detection of GAD Ab in the cerebrospinal fluid. Due to the relative rarity of these syndromes, treatment schemes and predictors of response are poorly defined, highlighting the unmet need for multicentric prospective trials in this population. Here, we reviewed the main clinical characteristics of neurological syndromes associated with GAD Ab, focusing on pathophysiologic mechanisms.

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Fulminant Anti-GAD antibody encephalitis presenting with status epilepticus requiring aggressive immunosuppression

Cited by 26 publications

References 28 publications

Stiff-person Syndrome and GAD Antibody-spectrum Disorders: GABAergic Neuronal Excitability, Immunopathogenesis and Update on Antibody Therapies

Stiff-person Syndrome and GAD Antibody-spectrum Disorders: GABAergic Neuronal Excitability, Immunopathogenesis and Update on Antibody Therapies

Thalamic Lesions in a Toddler with Glutamic Acid Decarboxylase Autoimmune Encephalitis

Neurological Syndromes Associated with Anti-GAD Antibodies

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