Are anti-glutamic acid decarboxylase 65-kDa isoform antibodies related to diabetes or brain tumor?

Abstract

Background Antibodies against the 65-kDa isoform of glutamic acid decarboxylase (GAD65) are biomarkers of autoimmune disorders and are more common in non-neurological autoimmune diseases than in neurological disorders. As for the central nervous system (CNS), it is well known that GAD65 is primarily associated with stiff-person syndrome, cerebellar ataxia, epilepsy, and paraneoplastic neurological syndrome. However, GAD65 antibodies have not been reported in patients with brain tumors. Case presentation This study presents the case of a 62-year-old man who manifested rapidly progressive dizziness with gradually worsening physical disturbance and unstable gait in the 2 months prior to consultation. Antibodies against GAD65 were detected in his serum. Brain magnetic resonance imaging (MRI) showed abnormal signals in the corpus callosum, the semi-oval center in both hemispheres, and the area below the frontal cortex, along with enhanced intracranial lesions in the same regions. Positron emission tomography–computed tomography (PET–CT) showed high metabolism in the corpus callosum, which protruded into both ventricles. Due to signs of malignancy, the patient was diagnosed with a malignant glioma. Conclusions This case raises awareness on the fact that anti-GAD65 antibodies may be associated with CNS neoplastic lesions. Early recognition of anti-GAD antibodies could be of great importance for the early diagnosis and targeted treatment of neoplastic lesions, and could lead to better prognosis.

Anti-Yo antibody-associated Autoimmune Encephalitis due to Breast Adenocarcinoma in a male patient

“…Although Gad65 positivity in our patient was associated with Diabetes Mellitus, it has been reported in the literature that Gad65 antibody may also be associated with cerebellar ataxia, epilepsy, brain stem syndromes, myelopathy, paraneoplastic neurological syndromes, and Gad65 may be associated with small cell or small cell lung cancer, lymphomas, neuroendocrine tumors and breast adenocarcinoma 13 . In addition, the literature has found that anti-titin antibodies can be associated with onconeuronal antibodies such as anti-Hu, Yo, Ri, Ma1, Ma2/Ta, CV2/CRMP5 and amphiphysin, which have been defined independently of myasthenia gravis, thymoma or thymic carcinoma.…”

An update on malignant tumor-related stiff person syndrome spectrum disorders: clinical mechanism, treatment, and outcomes

“…It is also associated with overlapping cancers, such as breast cancer with colon cancer ( 30 , 39 ), chronic lymphocytic leukemia ( 81 ), thymoma and non-Hodgkin lymphoma ( 80 ), non-functioning pituitary microadenoma, and endometrial cancer ( 29 ) ( Table 4 ). Table 5 shows the other carcinomas included in 25 studies involving six SPSSD subtypes, namely, classic SPS ( 21 – 36 ), SLS ( 86 , 90 ), PERM ( 91 ), progressive dizziness and unstable gait ( 87 ), and NMDAR-SPS ( 9 ). Furthermore, thyroid and renal cell cancers reportedly coexist with colon cancer and SPSSD ( 21 ).…”

“…The major SPSSD subtype is classic SPS ( 11 , 68 , 69 , 73 , 77 , 80 , 92 – 98 , 134 , 135 ), followed by SPS with myasthenia gravis ( 21 – 25 , 29 , 31 , 34 – 36 , 86 , 89 , 90 , 135 , 136 ), PERM ( 91 ), SLS ( 57 ), progressive dizziness and unstable gait ( 87 ), and NMDAR-SPS ( 9 ), as shown in Table 5 . Moreover, the major carcinoma associated with SPSSD subtypes is breast cancer ( 21 , 39 , 42 , 47 , 50 , 51 , 56 , 57 , 137 ), followed by thymoma ( 11 , 80 , 91 – 98 , 104 – 106 , 134 , 135 ), lymphoma ( 77 , 80 ), lung cancer ( 68 , 69 , 73 ), and other carcinomas ( 21 – 25 , 29 , 31 , 34 – 36 , 86 , 89 , 90 , 135 , 136 ).…”

“…SPSSD is also associated with other carcinomas, such as mediastinal liposarcoma ( 22 ), metastatic adenocarcinoma ( 23 ), pancreatic adenocarcinoma ( 24 ), renal cell carcinoma ( 25 ), mediastinal cancer, undifferentiated carcinoma of an undetermined origin ( 26 ), multiple myeloma ( 86 ), embryonal carcinoma ( 27 ), malignant glioma ( 87 ), ovarian adenocarcinoma ( 88 ), prostate carcinoma ( 88 ), testicular seminoma and germ cell neoplasia ( 88 ), pancreatic cancer ( 88 ), melanoma ( 88 ), an invasive carcinoma of no special type ( 28 ), ovarian teratoma ( 9 ), small cell carcinoma of the bladder ( 31 ), pleuropulmonary blastoma ( 33 ), malignant mesothelioma ( 35 ), colon cancer, and Hürthle cell adenoma ( 36 ). It is also associated with overlapping cancers, such as breast cancer with colon cancer ( 30 , 39 ), chronic lymphocytic leukemia ( 81 ), thymoma and non-Hodgkin lymphoma ( 80 ), non-functioning pituitary microadenoma, and endometrial cancer ( 29 ) ( Table 4 ).…”