Cognitive decline in a patient with anti-glutamic acid decarboxylase autoimmunity; case report

Abstract

BackgroundGlutamic acid decarboxylase (GAD) is the rate-limiting enzyme for producing γ-aminobutyric acid, and it has been suggested that antibodies against GAD play a role in neurological conditions and type 1 diabetes. However, it is not known whether dementia appears as the sole neurological manifestation associated with anti-GAD antibodies in the central nervous system.Case presentationWe describe the clinical, neuropsychological, and neuroradiological findings of a 73-year-old female with cognitive dysfunction and type 1A diabetes. Observation and neuropsychological studies revealed linguistic problems, short-term memory disturbance, and frontal dysfunction. MRI showed no significant lesion except for confluent small T2-hyperintensity areas localized in the left basal ganglia. 18F-fluorodeoxy glucose-positron emission tomography (FDG-PET) and 123I-N-isopropyl-p-iodoamphetamine-single photon emission computed tomography (IMP-SPECT) studies showed bifrontal hypometabolism and hypoperfusion. Immunomodulating therapy with intravenous high-dose immunoglobulin resulted in no remission of the cognitive symptoms.ConclusionsCognitive dysfunction may develop as an isolated neurological manifestation in association with type 1A diabetes and anti-GAD autoimmunity. A systematic study with extensive neuropsychological assessment is indicated in patients with type 1 diabetes and anti-GAD autoimmunity.

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

“…The only subtle neurological manifestation, other than cognitive impairment, was a disturbance in horizontal eye motion, which was noted in 2 patients in the GADA group. It was also noted in the patient with GADA-associated cerebellar ataxia, who was excluded from the present study, and our previously published case with GADA-positive diabetes and dementia [14]. Full range of motion and conjugate movement indicate preserved integrity of the neural pathway from the frontal eye field to the cranial nerves, but a difficulty in unilateral gaze-holding suggests a dysfunction of the cerebello-vestibular system [29].…”

“…Diabetic patients are at risk for dementia [9-11], especially vascular dementia, and Alzheimer’s disease [12,13]. We recently encountered a patient with GADA-positive diabetes who presented with language problems, short-term memory disturbance, and frontal dysfunction without any other neurological deficits, suggesting that GADA may cause dementia [14]. This observation led to the hypothesis that GADA cause cognitive deficits in patients with immune-mediated diabetes.…”

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

“…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 ].…”

“…Behavioral and cognitive impairments may also accompany anti-GAD-related neurological disorders. Previous studies have revealed that patients with both high (more than 2000 U/mL) and low (<100 U/mL) anti-GAD antibody levels may present with limbic symptoms [ 10 , 11 ]. Similarly, we identified a bipolar disorder patient with low anti-GAD antibody levels and no atypical features suggestive of autoimmune encephalitis.…”

Autoimmune epilepsy: findings on MRI and FDG-PET

“…This has been corroborated in a few case reports. 21,79 Anti-Hu antibody related AE The Hu antigen is found in the nucleus and cytoplasm of all neurons of the central and peripheral nervous system. 80 Anti-Hu antibody (ANNA-1), which incites a T-cell mediated attack, was the first onconeuronal antibody described.…”