Cognitive dysfunction associated with anti-glutamic acid decarboxylase autoimmunity: a case-control study

Takagi, Masahito; Ishigaki, Yasushi; Uno, Kenji; Sawada, Shojiro; Imai, Junta; Kaneko, Keizo; Yamada, Tetsuya; Tokita, Ai; Iseki, Kazuo; Kanno, Shigenori; Nishio, Yoshiyuki; Katagiri, Hideki; Mori, Etsuro

doi:10.1186/1471-2377-13-76

Cited by 21 publications

(14 citation statements)

References 37 publications

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“…Three of our patients reported progressive memory decline even when their epilepsy was well-controlled. Tagaki et al (41) conducted a case control study comparing cognitive performance of late-onset type one diabetic (LADA) patients with GAD ab and matched type 2 diabetes mellitus patients. They observed that verbal and visual test scores were lower in LADA+GAD ab patients and hypothesized that GAD-positive diabetic patients had an increased risk of cognitive decline compared to patients with type 2 diabetes of comparable diabetic severity.…”

Section: Discussionmentioning

confidence: 99%

Hippocampus and Insula Are Targets in Epileptic Patients With Glutamic Acid Decarboxylase Antibodies

et al. 2019

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Background: Antibodies to glutamic acid decarboxylase (GAD ab) have been found in patients with limbic encephalitis (LE) and chronic pharmacoresistant focal epilepsy (FE). The objectives of the study were to: (1) analyze the clinical and neuroimaging course of patients with FE+GAD ab, (2) compare these characteristics with a control group, and (3) describe the most affected cerebral areas with structural and functional imaging.Methods: Patients with FE + high titers of GAD ab and a follow-up of at least 5 years were selected. Titers of serum GAD ab exceeding 2,000 UI/ml were considered high. Evolutive clinical and radiological characteristics were studied in comparison to two different control groups: patients with bilateral or with unilateral mesial temporal sclerosis (BMTS or UMTS) of a non-autoimmune origin.Results: A group of 13 patients and 17 controls were included (8 BMTS, 9 UMTS). The most frequent focal aware seizures (FAS) reported by patients were psychic (5/13: 33%). Somatosensorial, motor, and visual FAS (4/13:32%) (p: 0.045), musicogenic reflex seizures (MRS), and a previous history of cardiac syncope were reported only patients (2/13:16% each) (p: NS). Comparing EEG characteristics between patients and controls, a more widespread distribution of interictal epileptiform discharges (IED) was observed in FE+ GAD ab patients than in controls (p:0.01). Rhythmic delta activity was observed in all controls in anterior temporal lobes while in patients this was less frequent (p: 0.001). No IED, even in 24 h cVEEG, was seen in 6 patients (46%).First MRI was normal in 4/5 (75%) patients. During the follow-up mesial temporal lobe (MTsL) sclerosis was observed in 5/8 (62%) of patients. All patients had abnormal FDG-PET study. MTL hypometabolism was observed in 10/11 (91%) patients, being bilateral in 7/11 (63%). In controls, this was observed in 16/17 (94%), and it was bilateral in 8/17 (47%) (p: NS). Insular hypometabolism was observed in 5/11 (45%) patients (P:0.002).Conclusions: Clinical, EEG, and FDG-PET findings in FE+GAD ab suggest a widespread disease not restricted to the temporal lobe. Progressive MTL sclerosis may be observed during follow-up. In comparison to what is found in patients with non-autoimmune MTL epilepsy, insular hypometabolism is observed only in patients with GAD ab, so it may be an important diagnostic clue.

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Section: Discussionmentioning

confidence: 99%

Hippocampus and Insula Are Targets in Epileptic Patients With Glutamic Acid Decarboxylase Antibodies

et al. 2019

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“…Our patient reported cognitive dysfunction which was associated with an increase of GAD antibodies. The presence of GAD antibodies is associated with worse cognitive performance despite the fact that epileptic seizures might also worsen cognition (3). Idiopathic generalized epileptiform seizures have been described in a girl with APECED (4), but GAD antibody-associated LE has not been reported in APECED patients so far.…”

Section: Discussionmentioning

confidence: 99%

GAD antibody-associated limbic encephalitis in a young woman with APECED

Kopczak

Schumacher²,

Nischwitz

et al. 2017

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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The autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) syndrome is a genetic disorder caused by a mutation in the autoimmune regulator (AIRE) gene. Immune deficiency, hypoparathyroidism and Addison’s disease due to autoimmune dysfunction are the major clinical signs of APECED. We report on a 21-year-old female APECED patient with two inactivating mutations in the AIRE gene. She presented with sudden onset of periodic nausea. Adrenal insufficiency was diagnosed by means of the ACTH stimulation test. Despite initiation of hormone replacement therapy with hydrocortisone and fludrocortisone, nausea persisted and the patient developed cognitive deficits and a loss of interest which led to the diagnosis of depression. She was admitted to the psychiatric department for further diagnostic assessment. An EEG showed a focal epileptic pattern. Glutamic acid decarboxylase (GAD) antibodies, which had been negative eight years earlier, were now elevated in serum and in the cerebrospinal fluid. Oligoclonal bands were positive indicating an inflammatory process with intrathecal antibody production in the central nervous system (CNS). The periodic nausea was identified as dialeptic seizures, which clinically presented as gastrointestinal aura followed by episodes of reduced consciousness that occurred about 3–4 times per day. GAD antibody-associated limbic encephalitis (LE) was diagnosed. Besides antiepileptic therapy, an immunosuppressive treatment with corticosteroids was initiated followed by azathioprine. The presence of nausea and vomiting in endocrine patients with autoimmune disorders is indicative of adrenal insufficiency. However, our case report shows that episodic nausea may be a symptom of epileptic seizures due to GAD antibodies-associated LE in patients with APECED.Learning points:Episodic nausea cannot only be a sign of Addison’s disease, but can also be caused by epileptic seizures with gastrointestinal aura due to limbic encephalitis.GAD antibodies are not only found in diabetes mellitus type 1, but they are also associated with autoimmune limbic encephalitis and can appear over time.Limbic encephalitis can be another manifestation of autoimmune disease in patients with APECED/APS-1 that presents over the time course of the disease.

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“…The key finding of our study was the clinical presentation of NMDAR antibody-associated autoimmune encephalitis masquerading as DLB, demonstrating the potential for misdiagnosis of a reversible condition as a progressive dementia syndrome. Cognitive impairment has been reported in association with several autoantibodies directed against neuronal antigens such as VGKC-complex [ 1 , 2 ], NMDAR [ 3 , 9 ], and GAD [ 10 , 11 ]. Anti-NMDAR encephalitis is particularly associated with psychiatric and neurological symptoms such as memory problems, seizures, hallucinations, and delusions [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Incidence and Clinical Features of Antibody-Associated Autoimmune Encephalitis Mimicking Dementia

Çoban

Küçükali

Bılgıç

et al. 2014

Behavioural Neurology

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Background. Anti-neuronal autoimmunity may cause cognitive impairment that meets the criteria for dementia. Objective. Our aim was to detect the incidence and clinical features of autoimmune encephalitis imitating clinical findings of primary dementia disorders and to delineate the validity of anti-neuronal antibody screening in dementia patients. Methods. Fifty consecutive patients fulfilling the clinical criteria for primary dementia, 130 control patients, and 50 healthy controls were included. Their sera were investigated for several ion channel and glutamic acid decarboxylase (GAD) antibodies by a cell-based assay, radioimmunoassay, and ELISA, as required. Results. Sixteen patients satisfying dementia criteria had atypical findings or findings suggestive of autoimmune encephalitis. N-methyl-D-aspartate receptor (NMDAR) antibody was detected in a patient with dementia, Parkinsonism, and REM sleep behavior disorder (RBD) fulfilling the criteria for dementia with Lewy bodies (DLB). One control patient with bipolar disease displayed low anti-GAD antibody levels. Conclusions. Our study showed for the first time the presence of parkinsonism and RBD in an anti-NMDAR encephalitis patient mimicking DLB. Although autoimmune encephalitis patients may occasionally present with cognitive decline, most dementia patients do not exhibit anti-neuronal antibodies, suggesting that routine analysis of these antibodies in dementia is not mandatory, even though they display atypical features.

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Cognitive dysfunction associated with anti-glutamic acid decarboxylase autoimmunity: a case-control study

Cited by 21 publications

References 37 publications

Hippocampus and Insula Are Targets in Epileptic Patients With Glutamic Acid Decarboxylase Antibodies

Hippocampus and Insula Are Targets in Epileptic Patients With Glutamic Acid Decarboxylase Antibodies

GAD antibody-associated limbic encephalitis in a young woman with APECED

Evaluation of Incidence and Clinical Features of Antibody-Associated Autoimmune Encephalitis Mimicking Dementia

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