Analysis of the clinical characteristics of 10 cases of serum anti-glutamic acid decarboxylase-65 antibody-positive autoimmune neurological diseases

Analysis of the clinical characteristics of 10 cases of serum anti-glutamic acid decarboxylase-65 antibody-positive autoimmune neurological diseases | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Analysis of the clinical characteristics of 10 cases of serum anti-glutamic acid decarboxylase-65 antibody-positive autoimmune neurological diseases Yujun Wu, Meng-meng Wang, Kai-li Jin, Li-yan Gu, Min-lu Wu, Ying Chen, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5351211/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective To study the clinical characteristics of patients with anti-glutamic acid decarboxylase-65 (GAD-65) antibody-positive autoimmune neurological diseases. Methods The clinical data of 10 patients with anti-GAD-65 antibody-positive autoimmune neurological diseases who were admitted to the department of neurology of NO. 905 Hospital of PLA Navy from November 2014 to November 2023 was retrospectively analyzed. Results The age of onset of 10 patients was 15 to 72 (44.9 ± 21) years old and the confirmed age was 21 to 73 (47.3 ± 20.1) years old. The ratio of male to female was 1:9. In three cases, symptoms were easily triggered by mental stress, fatigue and around the time of menstruation, and in one case, symptoms of muscle spasms were obvious at night. Clinical manifestations: 3 cases of single or double lower limb spasm with or without abdominal cramps, 3 cases of limb stiffness with swallowing or dyspnea or diplopia, 2 cases of unconsciousness, limb convulsions with memory loss, 1 case of dizziness, limb numbness and olfactory hallucinations, and 1 case of hiccups, nausea and vomiting. The final diagnosis was as follows: 6 cases of stiff-person syndrome (SPS), 2 cases of limbic encephalitis (LE) with seizures, 1 case of autoimmune encephalitis with cerebellar ataxia (CA), and 1 case of autoimmune brainstem cerebellum. In the auxiliary examination, 10 patients were positive for different titers of GAD65 in blood and/or cerebrospinal fluid (CSF), including 1 with GAD67 positive in CSF at the same time; 5 with abnormal blood autoimmune antibodies, 4 with abnormal thyroid function, 3 had diabetes and 2 with thymoma or thymic hyperplasia. Imagological examinations of the brain indicated that 3 patients had abnormal signals in hippocampus or temporal lobe; 2 had mild abnormal electroencephalogram (EEG) with no epileptiform discharge. In 6 cases, electromyography (EMG) showed continuous muscle motor unit electrical activity in the group of muscles at rest. 1 case had positive peroneal sensation in the right lower limbs, and 1 case showed cervicofacial abnormality and left ulnar nerve sensory positive. Treatments Except for the first patient who only received symptomatic treatment, the remaining 9 patients were immunoreacted. Among them, 3 patients were treated with first-line treatment alone, 6 patients received first-line combined with second-line treatment, and 4 patients with seizures were treated with antiepileptic drugs. Ten patients were followed up, one died half a year later, and the remaining nine had symptoms improved (mRS score ≧ 1 point). Conclusion Anti-GAD65 antibody encephalitis is more common in young and middle-aged people, more women than men. Its clinical manifestations mainly include SPS, CA, LE and so on. Given that single or multiple symptoms exist at the same time, high titer of GAD65 antibody in serum is the gold standard for diagnosis. Though epilepsy is often difficult to control, immunotherapy has a good effect on the vast majority of patients, and it should be started as soon as possible, which helps to improve the recovery. glutamic acid decarboxylase 65 stiff-person syndrome limbic encephalitis autoimmune encephalitis Figures Figure 1 Introduction Glutamic acid decarboxylase (GAD) is a rate-limiting enzyme for the synthesis of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) 1 . Anti-GAD 65 antibody has been implicated in a variety of conditions, including insulin-dependent diabetes mellitus (IDDM), stiff⁃person syndrome (SPS), cerebellar ataxia (CA), limbic encephalitis (LE) and autoimmune epilepsy 2 – 5 . GAD-65 antibody-related autoimmune neurological lesions are very rare in clinical practice, and the clinical symptoms are complex, and diverse. In this paper, we aim to improve the understanding of the disease and provide a basis for its early diagnosis and treatment by reviewing and summarizing the clinical data of 10 patients with anti-GAD-65 antibody-positive autoimmune neurological diseases who were admitted to the department of neurology of NO. 905 Hospital of PLA Navy from November 2014 to November 2023, analyzing and discussing the characteristics of the disease, and carrying out a clinical analysis with literature. Information and methods 1.1 Case data After collecting and retrospectively analyzing 10 patients with GAD65 antibody positive autoimmune neurological diseases who were admitted to the department of neurology of NO. 905 Hospital of PLA Navy from November 2014 to November 2023, we found the enrollment criteria were: ① Positive for serum GAD-65 antibody. ② The initial symptoms were neurological. And the exclusion criteria were: ① Positive for serum GAD-65 antibody but no neurological symptoms. ② Excluding other antibody-related immune neurological diseases. ③ Patients who do not cooperate with the examination and treatment. This study has been approved by the Ethics Committee of PLA Navy No.905 Hospital. The diagnostic criteria for SPS were described in the revised 2009 edition by Marinos C. Dalakas 7 , which mainly includes the following 6 articles: 1. Persistent stiffness and rigidity of the axial muscles (particularly the abdominal and thoracolumbar paravertebral muscles) often result in excessive lumbar anterior concave spine; 2. Sudden painful spasm: caused by voluntary movements, emotional disturbances, or unexpected auditory and somatosensory stimuli that lessen or disappear after sleep; 3. Continually motor unit activity (CMUA) occurs in a group of antagonistic muscles; 4. Lack of neurological findings suggestive of other diseases; 5. Evidence of positive serology: GAD autoantibodies confirmed by cytoimmunology, Western Blot or radioimmunology; 6. Being effective for diazepam treatment. 1.2 Study Methods 1.2.1 Test methods All patients were examined for blood, urine and fecal routine, liver and kidney function, electrolytes, blood glucose, blood erythrocyte sedimentation rate, thyroid function, tumor index, autoimmune antibodies, serum GAD antibody CBA titer, electrocardiogram, abdominal ultrasound, chest CT, head MRI and other tests. Among the 10 patients, 8 patients had undergone conventional, biochemical and cytological examination of cerebrospinal fluid, and 5 patients were sent for cerebrospinal fluid GAD antibody testing, as well as cerebrospinal fluid N-methyl-D aspartate receptor (NMDAR), GABA A antibody, contact protein related protein 2 (CASPR2), anti-α -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) type 1, leucine-rich glioma inactivated-1 protein (LGI-1) and other autoimmune encephalitis antibodies and anti-Amphiphysin antibodies, anti-PNMA2 (Ma2/Ta) antibodies, anti-CV2, Ri, Yo, Hu and other paraneoplastic antibodies testings. Medical School ethics committee provided approval (approval no 5107). Subjects or their next of kin provided informed consent for inclusion in the case series. 1.2.2 Data collection The gender, age, and course of the disease were collected, and the clinical manifestations, auxiliary examinations, treatment, and outcomes of the 110 patients enrolled were analyzed. Clinical manifestations include: initial symptoms, main symptoms and concomitant symptoms; and auxiliary examinations include: thyroid function, blood glucose, glycosylated hemoglobin, cerebrospinal fluid routine, biochemical, oligoclonal bands, electroencephalogram, electromyography, and cranial imaging. Treatments and prognosis were also reviewed and analyzed. The mean follow-up was 12 months. The modified Rankin scale (mRS) score was used to assess living ability, including three types of outcomes: disappearance of symptoms, improvement in symptoms (mRS score ≧ 1) and no relief in symptoms. Results 2.1 General data and clinical characteristics The 10 patients positive for GAD65 antibody were retrospectively collected, of which 9 were female and 1 was male. There were 6 cases of stiff-person syndrome, 2 cases of limbic encephalitis with seizures, 1 case of autoimmune encephalitis with cerebellar ataxia, and 1 case of autoimmune brainstem cerebellitis. The age of onset ranged from 15 to 72 (44.9 ± 21) years old, and the age of diagnosis was from 21 to 73 (47.3 ± 20.1) years old. Among the 10 patients, 3 symptoms were easily triggered by mental stress, fatigue and around the time of menstruation, and 1 case had obvious nocturnal onset of muscle spasms. Clinical manifestations: 3 cases of single or double lower limb spasm with or without abdominal cramps, 3 cases of limb stiffness with swallowing or dyspnea or diplopia, 2 cases of unconsciousness, limb convulsions with memory loss, 1 case of dizziness, limb numbness, olfactory hallucinations, and 1 case of hiccups, nausea and vomiting. The final diagnosis was as follows: 6 cases of stiff-person syndrome (SPS), 2 cases of limbic encephalitis (LE) with seizures, 1 case of autoimmune encephalitis with cerebellar ataxia (CA), and 1 case of autoimmune brainstem cerebellum. Among the comorbidities, 5 were associated with abnormal blood autoimmune antibodies, 4 with abnormal thyroid function, 3 had diabetes mellitus, 2 with thymoma or thymic hyperplasia, 1 had vitiligo and 1 had hypertension. See Table 1 for details. Table 1 Clinical data of 10 patients with serum GAD 65 No. sex Age Onset Age clinical manifestation diagnose predisposition symptom Concomitant disease 1 M 73y 72 nervous tired abdominal spasms, spasms of both lower limbs, stiffness and sweating - SPS 2 F 66y 66 - stiff limbs and dysphagia hypertension SPS 3 F 45y 43 - stiffness and spasms in the right lower extremity DM; thyroid dysfunction; nRNP/Sm(+); ANA: 1:100(+) SPS 4 F 64y 61y night throbbing pain, cramp and stiffness in both lower limbs DM; Vitiligo; thyroid dysfunction; SSA(60)+ SPS 5 F 21y 15y menstruation nervous inawareness, limbs twitching and memory loss hashimoto's thyroiditis LE 6 F 34y 32y - dizziness, limb numbness and olfactory hallucinations DM; ANA: 1:100(+) AE 7 F 71y 71y - stiff limbs and dyspnea thymoma (type B1); cervical carcinoma SPS 8 F 41y 31y nervous diplopia, stiff limbs SCH; ANA 1:320(+); ACA IgM(+) SPS 9 F 42y 42y poor awareness, twitching of limbs and memory loss SSA(60)+ LE 10 F 16y 16y burping, nausea, and vomiting thymic hyperplasia AE Abbreviations: M: male; F: female; SPS: stiff-person syndrome; LE: limbic encephalitis; AE: autoimmune encephalitis; ANA: anti-nuclear antibody; DM: diabetes mellitus; SCH: subclinical hypothyroidism; ACA: anticardiolipin antibody 2.2 Auxiliary inspection 2.12 Laboratory examination Blood GAD antibodies were tested in all 10 patients and GAD-65 was positive (the first 2 patients were treated with western blot assay (WBA) method and the titer could not be mmeasured. And the last 8 patients were treated with Cytometric Bead Array (CBA), and the GAD-65 titers were 1:100, 1:1000, 1:1000, 1:3200, 1:1000, 1:3200, 1:1000, 1:320 respectively). The ratio of neutrophil/lymphocyte ranged from 1.35 to 9.75; there were 4 cases with hemoglobin lower than normal, and they were anemia of different degrees, all of which were iron deficiency anemia; all the platelets were normal; only 1 case had a mild increase in C-reactive protein; there were 2 cases of elevated erythrocyte sedimentation rate, and both patients were negative for autoimmune antibodies; there were 2 cases of elevated immunoglobulin G, one of which was 1:320 positive for antinuclear antibody, and positive for anticardiolipin antibody IgM, but both cases were normal for immunoglobulin A; the immunoglobulin M was elevated in 1 case with nRNP/Sm positive in ENA and antinuclear antibody 1:100 positive in ANA; the immunoglobulin IgE was increased in 2 cases; complement C3 was decreased in 7 cases; complement C4 was all normal; the serum glutamyl transpeptidase was elevated in 4 cases; ceruloplasmin was decreased in 5 cases; hepatitis B antibody was positive in 7 cases; transferrin was reduced in 7 cases; vitamin B6 was reduced in 7 cases; total cholesterol and triglycerides were increased in an older patient, LDL was all normal; blood potassium and blood sodium were all normal; blood calcium was decreased in 1 older patient; glycosylaed hemoglobin was increased in 1 older patient; 4 patients were positive for thyroid antibodies; 9 were positive for fecal transferrin, which may be related to hormonal therapy; 1 case was positive for nRNP/Sm, 1:100 positive for antinuclear antibody; 2 cases were positive for SSA (60); 1 case was 1:320 positive for antinuclear antibody,and was positive for anticardiolipin antibody IgM ; 1 case was 1:100 positive for anti-nuclear antibody nuclear granular type; blood homocysteine was all normal; the D-dimers were all normal; . CSF Results: there were 8 patients who underwent lumbar puncture, 5 patients sent cerebrospinal fluid GAD antibodies, and the GAD65 in CSF of 5 patients was positive, and the titers were 1:100,1:320,1:100,1:32 and 1:32 respectively, among which patient 6’s GAD65 1:100 (+) was combined with GAD67 1:30 (+); 4 patients were sent for paratumor antibody and autoimmune encephalitis antibody tests at the same time, and the results were all negative. The number of CSF cells ranged from 0 to 6, sugar cells ranged from 2.88 to 7.2, and protein ranged from 0.12 to 0.38 in 5 patients, indicating that the cerebrospinal fluid routine and biochemistry were normal or mildly altered. 2.2.2 Electroencephalogram and electromyography examination All 10 patients had EEG examination in the acute stage. Among them, 2 patients had mildly abnormal EEG, and the frontal and whole brain were scattered in theta band power enhancement with no epileptiform discharge. All 6 patients diagnosed with stiff-person syndrome underwent EMG examination, and the characteristic changes of continuous muscle motor unit electrical activity (CMUA) were seen in the group of muscles at rest. 1 case was combined with positive superficial peroneal sensation in the right lower limb, positive median sensation in both upper limbs, and 1 case was suggestive of cerocacral abnormality, and positive ulnar nerve sensation in the left side. 2.2.3 radiographic examination All 10 cases had head magnetic resonance imaging (MRI), among which the 5 th , 6 th and 9 th cases underwent cranial TSPO, PRT-CT and/or FDG-PET examinations: one case had uneven and slightly elevated TSPO distribution on the medial temporal lobe on both sides, and the left side was obvious; one case had high metabolism of the left amygdala and left hippocampus on PET-CT; FDG metabolism in one case decreased on the medial frontal lobe of both sides. Whole-body PET-CT was performed in the 8 th patinet and no obvious abnormalities were found. Cranial MRI or PETT-CT examination indicated that there were 3 cases of abnormal signals in the hippocampus or temporal lobe, as shown in Table 2. 3.2 Follow-up visits and results 9 out of 10 patients received immunotherapy (the first case only received symptomatic treatment: clidazepam, baclofen, immunotherapy was refused, so he died six months later, and he was also the oldest, indicating that the elderly do not recover well without timely diagnosis and treatment,and early immunotherapy is crucial), among which 3 cases were treated with first-line treatment alone (the 2 th and 10 th case: r-globulin, the 4 th and 9 th case: methylprednisolone, r-globulin, plasma exchange), and the 5 th case of first-line combined with second-line treatment (the 3 th case: methylprednisolone, r-globulin and mycophenolate mofetil; the 5 th case: methylprednisolone, ketotezomib and cyclophosphamide; the 6 th case: methylprednisolone, r-globulin, azathioprine; the 7 th case: methylprednisolone, r-globulin and Ofa tolimab; the 8 th case: methylprednisolone, r-globulin and mycophenolate mofetil). Four cases received antiepileptic drugs, and three of them required a combination of two or more antiepileptic drugs. Ten patients were followed up, one died half a year later, the other 9 had improved symptoms (mRS score≧1 point), and one left right ankle and foot deformities, as detailed in Table 2. Table 2 Examinations and treatments of 10 patients with serum GAD 65 NO. Antibody titer Accessory examination Treatment Outcome blood CSF 1 GAD65 (BLOT): Positive ND Cranial MRI (-). CZP; BCF. die 2 GAD65 (BLOT): Positive ND Cranial MRI (-). IVIG. turn better 3 GAD65(CBA) 1:100 ND Cranial MRI (-). MPPT; IVIG; MMF. turn better 4 GAD65 (CBA) 1:1000 + ND Cranial MRI (-). MPPT; IVIG; PE. partial remission, leaving right ankle and foot deformity 5 GAD65 (CBA) 1:1000 + ND Cranial MRI (-); uneven and slightly elevated TSPO in bilateral medial temporal lobes. MPPT, ketotezomib; RTX. turn better 6 GAD65 (CBA) 1:1000 + GAD65 (CBA)：1:100+； GAD67 (CBA) 1:30+ Cranial MRI and PET-CT showed abnormalities in left temporal pole and hippocampus; Abnormal EEG. MPPT; IVIG; AZP. turn better 7 GAD65 (CBA) 1:3200 + GAD65 (CBA)：1:320+ Cranial MRI (-); MPPT; IVIG; kesimpta. turn better 8 GAD65 (CBA) 1:3200 + GAD65 (CBA)：1:100+ Cranial MRI (-); PET-CT (-). MPPT; IVIG; MMF. turn better 9 GAD65 (CBA) 1:1000 + GAD65 (CBA)：1:32+ Cranial MRI (-); FDG metabolism of bilateral medial frontal decreased. MPPT; IVIG; PE. turn better 10 GAD65 (CBA) 1:320 GAD65 (CBA)：1:32+ Cranial MRI (-). IVIG. turn better Note: CSF: Cerebrospinal fluid; WBA: Western blot assay; CBA: Cytometric Bead Array; ND: Not done; MRI: magnetic resonance imaging; PET-CT: Positron Emission Tomography-Computed Tomography; FDG: fluorodeoxyglucose; EEG: electroencephalo-graph; CZP: clonazepam; BCF: baclofen; IVIG: Intravenous immunoglobulin; MPPT: Methylprednisolne pluse therapy; MMF: Mycophenolate Mofetil; PE: plasma exchange; RTX: rituximab; AZP: azathioprim; (-): no significant abnormalities. Discussion Glutamic acid decarboxylase (GAD), first reported in the New England Journal of Medicine in 1988, is a rate-limiting enzyme in the formation of γ -aminobutyric acid (GABA) 7 . GAD antibodies can block GABA synthesis either by inhibiting GAD enzymatic activity or by blocking GAD 65-mediated vesicle trafficking 1 , which has been implicated in a variety of neurological syndromes, including SPS, CA, LE, palatine myoclonus, nystagmus, epilepsy and so on, which can occur simultaneously with one or more conditions 8 . Of the 8 patients in this study, 6 cases were SPS, 1 case was LE with seizures, 1 case was LE with C, and 1 case was autoimmune encephalitis with brainstem cerebellia. GAD antibody configurations include GAD65 and GAD67, which are respectively encoded by different chromosomal genes, and have 71% homology in the C-terminal domain and cofactor-binding region 9 . GAD 65 is mainly distributed on synaptic vesicles, mediating the transient synthesis of GABA under acute demand stress and promoting the transfer of synaptic vesicles to synaptic terminals 10 . The detection of GAD67 in peripheral blood or CSF depends on the presence of GAD65 antibody. It does not exist alone and its titer is often lower than that of GAD65, and it is usually not pathogenic 11 . In this paper, case 6 had a 1:100 (+) GAD65 antibody in the cerebrospinal fluid and a 1:30 positive GAD67 antibody was detected, and GAD65 was considered responsible for the disease. GAD65-positive autoimmune nervous system disease is more common in women, which can occur at different ages and are mostly subacute with prodromal symptoms such as headache, fever, dizziness, diplopia, etc. Clinical manifestations can include seizures, cognitive decline, mental and behavioral abnormalities, ataxia, dysarthria, movement disorders, involuntary movements and decreased level of consciousness, etc 12-14 . In this article, the male-to-female ratio of 10 patients was 1:9, among which 2 cases could be triggered by mental tension or menstrual period, 1 case with muscle spasm was more obvious at night, and 2 cases with precursor symptoms such as dizziness and diplopia. Clinical manifestations include: spasm of both lower limbs, laryngeal muscle spasm, abdominal spasm, epilepsy with memory loss, olfactory hallucinations, dizziness, hiccup with diplopia, etc. Brain MRI is one of the most commonly used detection techniques for diagnosing GAD65-positive autoimmune neurological disease, and some literature has pointed out that brain MRI is slightly different in the different courses of GAD 65 related encephalopathy, and in some cases, there is no obvious abnormality in the early stage of brain MRI, and in some patients, one or more intracranial lesions can be seen on brain MRI, especially in the limbic system 15 . In addition, with the development of imaging techniques, TSPO, FDG-PET and other examinations have been successively used in the diagnosis of neurological disease 16-18 . All 10 patients had head magnetic resonance (MRI), and 1 case had abnormal signals in the hippocampus or temporal lobe. Among them, case 5 was examined by cranial TSPO and FDG-PET, and the distribution of TSPO in both medial frontal lobes was uneven and slightly increased, which was obvious on the left side; the bilateral medial frontal FDG metabolism was decreased. Case 8 underwent a systemic PET-CT, with no obvious abnormalities. It is suggested that imaging examinations such as MRI, TAPO and FDG-PET have certain diagnostic significance for GAD65-positive autoimmune neurological diseases. Similar to the literature 8 , the cell number and protein in CSF of 8 patients were essentially normal with positive intrathecal synthesis of anti-GAD65 antibody. The most of the EEG tests were normal, 2 cases were mildly abnormal, and the frontal and whole-brain were scattered in the theta band power enhancement, and no epileptiform discharges were found. The literature has pointed out that some patients may also have unilateral or bilateral diffuse slow waves and sharp slow waves in the frontotemporal areas on EEG, which has certain suggestive significance for diagnosis. The diagnosis of GAD-65 disease mainly depends on the detection of CSF and serum GAD antibody. In this paper, serum GAD-65 antibody was all positive, the results of CSF GAD65 antibody were all positive in 5 cases, and the positive rate of CSF was lower than that of seroprevalenc 19,20 。 Anti-GAD65 antibodies are a biological marker of autoimmunity in central nervous system and non-neurological diseases. GAD65 is common in non-neurological autoimmune diseases, including type 1 diabetes, autoimmune thyroid disease and pernicious anemia. Thyroiditis is common, usually with a personal or family history of autoimmunity 21,22 . In addition to GAD65 pathogenic antibodies, it can coexist with other kinds of autoantibodies, such as anti-NMDAR, anti-GABAA, anti-LGI1DR, as well as paraneoplastic antibodies, while positive multiple anti-neuronal antibodies can lead to changes or superposition of clinical symptom 21,22 . In addition to GAD65 pathogenic antibodies, it can coexist with other kinds of autoantibodies, such as anti-NMDAR, anti-GABAA, anti-LGI1DR, as well as paraneoplastic antibodies, while positive multiple anti-neuronal antibodies can lead to changes or superposition of clinical symptoms 18,24,25 . Therefore, to establish the pathogenic link between GAD65 antibody and disease, it is necessary to exclude the influence of other antibody. Graus scholars pointed out that firstly, there is a high level of GAD65 antibody in serum, and secondly, GAD65 antibody is also present in cerebrospinal fluid, and it needs to be proven that the antibody is synthesized intrathecally 26 . In seven patients, high titers of GAD65 antibodies were present in both serum and cerebrospinal fluid , supporting the pathogenicity of GAD65 antibodies; 3 patients with complicated diabetes mellitus, 3 patients with positive thyroid antibodies (thyroglobulin antibodies, anti-thyroid myeloperoxidase), 4 patients with different degrees of anemia (hemoglobin minimum 83), 5 patients with positive autoimmune antibodies (2 cases with positive SSA antibodies , 1 case was 1:100 positive for anti-nuclear antibody nuclear granular type, 1 case was 1:100 positive for anti-nuclear antibody and nRNP / Sm, and 1 case was 1:320 positive for anti-nuclear antibody and anti-cardiolipin antibody IgM). Although the autoimmune nature of GAD65 antibodies is usually non-neoplastic, the possibility of cancer cannot be completely ruled out, especially in people at high risk of cancer, such as those with a family history of cancer or a high suspicion of cancer. It has been noted in the literature that GAD65 associated stiff-person syndrome can be accompanied by a variety of cancers such as small cell lung cancer and breast cancer 27 , and it has also been reported to be combined with thymic tumors,and its symptoms can be completely resolved after thymectomy (complex autoimmune disorder [J].J NeurolNeurosurg Psychiatry, 2015,86(8):840-848.）.Studies have identified GAD as the main autoantigens of type 1 diabetes, and it can also be ectopically transcribed and expressed in specific cell populations of the thymus 28 , Thymic dysfunction can play an important role in the development of type 1 diabetes 29 ; Additional studies pointed out that GAD65 can also promote the expression of inflammatory cytokines IFN- γ and IL-10 mRNA in vitro cultured thymocytes, suggesting that the GAD 65 antibodies are closely related to the thymus 30 . In this paper, one patient had two thymic and pleural metastasis surgeries, and the postoperative pathology was thymoma (type B1), and one patient had thymic hyperplasia. Both patients underwent thymectomy, and the symptoms were completely relieved after surgery. It suggests that thymic dysfunction may play a role in GAD65 antibody-positive autoimmune neurological disease, and surgical resection of the tumor may benefit in patients with GAD65 antibody disease with thymic hyperplasia or tumors. The pathogenicity of GAD antibodies remains controversial, and some studies indicate that GAD antibodies are mainly through T cell-mediated immune response indicators 31 . In contrast, a small number of studies have confirmed that intrathecal injection of GAD antibodies in patients with SPS or CA is sufficient to reproduce typical disease manifestations in animal models, supporting the hypothesis that GAD-Ab may exhibit a direct pathogenic mechanism 32,33 . Further studies have found that CSF GAD65-Abs can cross-react with muscle cell membranes, suggesting that GAD65-Abs may directly bind to receptors on muscle cell membranes in the same way as antigen-antibody reactions, thus playing an important role in muscle movement regulation 34 . The treatment of GAD65 antibody-positive autoimmune neurological diseases is still dominated by immunotherapy, including high-dose intravenous prednisolone pulse, intravenous immunoglobulin (IVIG) injection, and plasmapheresis in the acute phase, and the recovery period includes oral methylprednisolone, immunosuppressants, and rituximab to prevent recurrence in the convalescent phase 35 . Clinical experience shows that initiating immunotherapy as soon as possible in the early stage of the disease is crucial for good recovery, and patients who do not accept immunotherapy have poor outcomes. The 1th Patient died half a year after receiving no immunotherapy, and the last 9 patients started immunotherapy immediately after diagnosis, except for the 4 th patient who had a long course of disease, older age, and more underlying diseases, and limited improvement in clinical symptoms after immunotherapy, leaving right ankle and foot deformities, the remaining 8 cases were significantly improved. Conclusion Anti-GAD65 antibody encephalitis is more common in young and middle-aged people, more women than men, and the clinical manifestations mainly include SPS, LE, AE, etc., and single or multiple symptoms exist at the same time. High titer of GAD65 antibody in serum is the gold standard for diagnosis. As epilepsy is often difficult to control, immunotherapy has a good effect on the vast majority of patients. Early diagnosis and prompt initiation of immunotherapy are essential to improve clinical symptoms and reduce recurrence and permanent disability. Therefore, attention should be paid to timely diagnosis and the implementation of appropriate treatment to obtain a better recovery for patients. Declarations Funding assistance This study was supported by the Scientific Project of NO 905 Hospital of PLA Naval (2021 X003), the Zhuyuan Scientific Project of the Nursing School of Naval Medical University (2022KYZ09), the Outstanding Young Talents Training Project of Naval Medical Center (21TPQN2701) and the "Qiang-Ji" project of Naval Medical Center (23M2701). Ethics approval and consent to participate Patients or their next of kin provided informed consent for inclusion in the case series and the aims of the study completely explained. Conflict of interest All authors have no conflicts of interest to report. Acknowledgements Not applicable. Author contributions YJW, MMW and KLJ: Investigation, Conceptualization, Writing-Original Draft, Writing-Review and Editing. LYG, MLW and YC: Investigation, Writing-Original Draft. 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Blood and CSF anti-neuronal antibodies testing in psychotic syndromes: a retrospective analysis from a tertiary psychiatric hospital.2024. Musso G, Zoccarato M, Gallo N, et al. Analytical evaluation of a GAD65 antibodies chemiluminescence immunoassay for CSF in neurological syndromes.2023;61(10):1802-1807. Vogrig A, Gigli G, Nilo A, Pauletto G, Valente MJB. Seizures, Epilepsy, and NORSE Secondary to Autoimmune Encephalitis: A Practical Guide for Clinicians.2022;11(1). Sapana T, Li W, Tian F, et al.A case report of anti-GAD65 antibody-positive autoimmune encephalitis in children associated with autoimmune polyendocrine syndrome type-II and literature review.2023;14:1274672. Graber JJC. Paraneoplastic Neurologic Syndromes.2023;29(6):1779-1808. Fang Y, Wu H, Liu G, et al. Secondary immunoreaction in patients with neurosyphilis and its relevance to clinical outcomes.2023;14:1201452. Nagata N, Kanazawa N, Mitsuhata T, et al. Neuronal surface antigen-specific immunostaining pattern on a rat brain immunohistochemistry in autoimmune encephalitis.2022;13:1066830. Graus F, Saiz A, Dalmau J.GAD antibodies in neurological disorders-insights and challenges[J].Nat Rev Neurol,2020,16(7): 353-365. Graus F, Vogrig A, Muñiz-Castrillo S, et al. Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes.2021;8(4). Maemura K, Yanagawa Y, Obata K, et al. Antigen-presenting cells expressing glutamate decarboxylase 67 were identified as epithelial cells in glutamate decarboxylase 67-GFP knock-in mouse thymus.2006;67(3):198-206. Geenen V, Brilot F, Louis C, Hansenne I, Renard C, Martens HJRmdL.[Importance of a thymus dysfunction in the pathophysiology of type 1 diabetes].2005;60:291-296. Bieg S, Möller C, Olsson T, Lernmark AJD. The lymphopenia (lyp) gene controls the intrathymic cytokine ratio in congenic BioBreeding rats.1997;40(7):786-792. Jing Y, Kong Y, McGinty J, et al.T-Cell Receptor/HLA Humanized Mice Reveal Reduced Tolerance and Increased Immunogenicity of Posttranslationally Modified GAD65 Epitope.2022;71(5):1012-1022. Hansen N, Grünewald B, Weishaupt A, et al. Human Stiff person syndrome IgG-containing high-titer anti-GAD65 autoantibodies induce motor dysfunction in rats.2013;239:202-209. Ali F, Rowley M, Jayakrishnan B, Teuber S, Gershwin M, Mackay IJJoa. Stiff-person syndrome (SPS) and anti-GAD-related CNS degenerations: protean additions to the autoimmune central neuropathies.2011;37(2):79-87. Zhang H, Yue J, Lian C, Long Y, He DJFii. Case Report: Extraocular muscles paralysis associated with GAD65 antibody: a case series study.2023;14:1256089. Amaia, Muñoz-Lopetegi, Marienke AAM, de Bruijn, et al. Neurologic syndromes related to anti-GAD65: Clinical and serologic response to treatment[J]. Neurol Neuroimmunol Neuroinflamm, 2020, 7: 0. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5351211","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":372326114,"identity":"6e4f28f8-60cd-4449-86e1-0dfdd615c321","order_by":0,"name":"Yujun Wu","email":"","orcid":"","institution":"NO 905 Hospital of PLA Naval","correspondingAuthor":false,"prefix":"","firstName":"Yujun","middleName":"","lastName":"Wu","suffix":""},{"id":372326115,"identity":"3bc1e54a-f5b3-4bd0-815d-2b49861f071b","order_by":1,"name":"Meng-meng Wang","email":"","orcid":"","institution":"Naval Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Meng-meng","middleName":"","lastName":"Wang","suffix":""},{"id":372326116,"identity":"994caf69-f31d-4025-bded-3d7cbc13b217","order_by":2,"name":"Kai-li Jin","email":"","orcid":"","institution":"Naval Medical University","correspondingAuthor":false,"prefix":"","firstName":"Kai-li","middleName":"","lastName":"Jin","suffix":""},{"id":372326117,"identity":"cb00dc5e-ba92-4264-94f8-d174390fe8cd","order_by":3,"name":"Li-yan Gu","email":"","orcid":"","institution":"NO 905 Hospital of PLA Naval","correspondingAuthor":false,"prefix":"","firstName":"Li-yan","middleName":"","lastName":"Gu","suffix":""},{"id":372326118,"identity":"3be6401c-12a6-4bec-95df-96951ffb0cf6","order_by":4,"name":"Min-lu Wu","email":"","orcid":"","institution":"NO 905 Hospital of PLA Naval","correspondingAuthor":false,"prefix":"","firstName":"Min-lu","middleName":"","lastName":"Wu","suffix":""},{"id":372326119,"identity":"3f5e96b2-6dd5-4db5-872e-88b52b7817bc","order_by":5,"name":"Ying Chen","email":"","orcid":"","institution":"Naval Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Ying","middleName":"","lastName":"Chen","suffix":""},{"id":372326120,"identity":"3b782b6c-43bb-467a-b5d0-c158cb9142e3","order_by":6,"name":"Yi Han","email":"","orcid":"","institution":"Naval Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Han","suffix":""},{"id":372326121,"identity":"e357c6b0-cfa7-4082-b5b1-6c0c44ff097c","order_by":7,"name":"Jie Wei","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIie3PsWoCQRCA4VkWtrrk2hHEvMKKIHb6KLMIVymkvEKSC4pbeHrtQfIQlpZrs9XaX7k+gl3ShNgnuJfOYr96fmYGIIrukEgrb9Q3vr7p6uIpX4STR3TMezFiy9IMpHc2nPRgxvte5EzXk2HnvOItDoOTRUqQP9SQ5aoQkOoN3U74LkNCFJ33wjbq0AV0p31gixkiSUz6H8d1o5wAifNQQtfkumbcTMWzWvM2yWwgyaBkdSagXYJWeVUgsdJxJGeT4C9P1dIcv4oXYrpkl8980Uv19nbyS/K/8SiKouhPP+nhSv/BPSrLAAAAAElFTkSuQmCC","orcid":"","institution":"NO 905 Hospital of PLA Naval","correspondingAuthor":true,"prefix":"","firstName":"Jie","middleName":"","lastName":"Wei","suffix":""}],"badges":[],"createdAt":"2024-10-29 05:23:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5351211/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5351211/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":70037794,"identity":"3563da36-da3a-40a7-a4db-f52f4c804092","added_by":"auto","created_at":"2024-11-27 17:28:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":114622,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRadiographic examination of the 5\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003eth\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e and 6\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003eth\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e patients with serum GAD 65\u003c/strong\u003e (A1, A2): uneven and slightly elevated TSPO in bilateral medial temporal lobes; PET-CT showed abnormalities in left temporal pole (B1) and hippocampus (B2).\u003c/p\u003e","description":"","filename":"Figure.1.png","url":"https://assets-eu.researchsquare.com/files/rs-5351211/v1/8999f803a0060ec7d8bc3a48.png"},{"id":70039314,"identity":"244a6165-6fbd-4785-973d-cf1772e13367","added_by":"auto","created_at":"2024-11-27 17:44:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":649583,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5351211/v1/a9c8be83-8330-40a6-92b3-0b7598751731.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Analysis of the clinical characteristics of 10 cases of serum anti-glutamic acid decarboxylase-65 antibody-positive autoimmune neurological diseases","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGlutamic acid decarboxylase (GAD) is a rate-limiting enzyme for the synthesis of the inhibitory neurotransmitter γ-aminobutyric acid (GABA)\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Anti-GAD 65 antibody has been implicated in a variety of conditions, including insulin-dependent diabetes mellitus (IDDM), stiff⁃person syndrome (SPS), cerebellar ataxia (CA), limbic encephalitis (LE) and autoimmune epilepsy\u003csup\u003e\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. GAD-65 antibody-related autoimmune neurological lesions are very rare in clinical practice, and the clinical symptoms are complex, and diverse. In this paper, we aim to improve the understanding of the disease and provide a basis for its early diagnosis and treatment by reviewing and summarizing the clinical data of 10 patients with anti-GAD-65 antibody-positive autoimmune neurological diseases who were admitted to the department of neurology of NO. 905 Hospital of PLA Navy from November 2014 to November 2023, analyzing and discussing the characteristics of the disease, and carrying out a clinical analysis with literature.\u003c/p\u003e"},{"header":"Information and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e1.1 Case data\u003c/h2\u003e \u003cp\u003eAfter collecting and retrospectively analyzing 10 patients with GAD65 antibody positive autoimmune neurological diseases who were admitted to the department of neurology of NO. 905 Hospital of PLA Navy from November 2014 to November 2023, we found the enrollment criteria were: ① Positive for serum GAD-65 antibody. ② The initial symptoms were neurological. And the exclusion criteria were: ① Positive for serum GAD-65 antibody but no neurological symptoms. ② Excluding other antibody-related immune neurological diseases. ③ Patients who do not cooperate with the examination and treatment. This study has been approved by the Ethics Committee of PLA Navy No.905 Hospital. The diagnostic criteria for SPS were described in the revised 2009 edition by Marinos C. Dalakas\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e, which mainly includes the following 6 articles: 1. Persistent stiffness and rigidity of the axial muscles (particularly the abdominal and thoracolumbar paravertebral muscles) often result in excessive lumbar anterior concave spine; 2. Sudden painful spasm: caused by voluntary movements, emotional disturbances, or unexpected auditory and somatosensory stimuli that lessen or disappear after sleep; 3. Continually motor unit activity (CMUA) occurs in a group of antagonistic muscles; 4. Lack of neurological findings suggestive of other diseases; 5. Evidence of positive serology: GAD autoantibodies confirmed by cytoimmunology, Western Blot or radioimmunology; 6. Being effective for diazepam treatment.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e1.2 Study Methods\u003c/h3\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e1.2.1 Test methods\u003c/h2\u003e \u003cp\u003eAll patients were examined for blood, urine and fecal routine, liver and kidney function, electrolytes, blood glucose, blood erythrocyte sedimentation rate, thyroid function, tumor index, autoimmune antibodies, serum GAD antibody CBA titer, electrocardiogram, abdominal ultrasound, chest CT, head MRI and other tests. Among the 10 patients, 8 patients had undergone conventional, biochemical and cytological examination of cerebrospinal fluid, and 5 patients were sent for cerebrospinal fluid GAD antibody testing, as well as cerebrospinal fluid N-methyl-D aspartate receptor (NMDAR), GABA\u003csub\u003eA\u003c/sub\u003e antibody, contact protein related protein 2 (CASPR2), anti-α -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) type 1, leucine-rich glioma inactivated-1 protein (LGI-1) and other autoimmune encephalitis antibodies and anti-Amphiphysin antibodies, anti-PNMA2 (Ma2/Ta) antibodies, anti-CV2, Ri, Yo, Hu and other paraneoplastic antibodies testings. Medical School ethics committee provided approval (approval no 5107). Subjects or their next of kin provided informed consent for inclusion in the case series.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e1.2.2 Data collection\u003c/h3\u003e\n\u003cp\u003eThe gender, age, and course of the disease were collected, and the clinical manifestations, auxiliary examinations, treatment, and outcomes of the 110 patients enrolled were analyzed. Clinical manifestations include: initial symptoms, main symptoms and concomitant symptoms; and auxiliary examinations include: thyroid function, blood glucose, glycosylated hemoglobin, cerebrospinal fluid routine, biochemical, oligoclonal bands, electroencephalogram, electromyography, and cranial imaging. Treatments and prognosis were also reviewed and analyzed. The mean follow-up was 12 months. The modified Rankin scale (mRS) score was used to assess living ability, including three types of outcomes: disappearance of symptoms, improvement in symptoms (mRS score\u0026thinsp;≧\u0026thinsp;1) and no relief in symptoms.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\"\u003e\n \u003ch2\u003e2.1 General data and clinical characteristics\u003c/h2\u003e\n \u003cp\u003eThe 10 patients positive for GAD65 antibody were retrospectively collected, of which 9 were female and 1 was male. There were 6 cases of stiff-person syndrome, 2 cases of limbic encephalitis with seizures, 1 case of autoimmune encephalitis with cerebellar ataxia, and 1 case of autoimmune brainstem cerebellitis. The age of onset ranged from 15 to 72 (44.9\u0026thinsp;\u0026plusmn;\u0026thinsp;21) years old, and the age of diagnosis was from 21 to 73 (47.3\u0026thinsp;\u0026plusmn;\u0026thinsp;20.1) years old. Among the 10 patients, 3 symptoms were easily triggered by mental stress, fatigue and around the time of menstruation, and 1 case had obvious nocturnal onset of muscle spasms. Clinical manifestations: 3 cases of single or double lower limb spasm with or without abdominal cramps, 3 cases of limb stiffness with swallowing or dyspnea or diplopia, 2 cases of unconsciousness, limb convulsions with memory loss, 1 case of dizziness, limb numbness, olfactory hallucinations, and 1 case of hiccups, nausea and vomiting. The final diagnosis was as follows: 6 cases of stiff-person syndrome (SPS), 2 cases of limbic encephalitis (LE) with seizures, 1 case of autoimmune encephalitis with cerebellar ataxia (CA), and 1 case of autoimmune brainstem cerebellum. Among the comorbidities, 5 were associated with abnormal blood autoimmune antibodies, 4 with abnormal thyroid function, 3 had diabetes mellitus, 2 with thymoma or thymic hyperplasia, 1 had vitiligo and 1 had hypertension. See Table \u003cspan\u003e1\u003c/span\u003e for details.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1 Clinical data of 10 patients with serum GAD 65\u003c/strong\u003e\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"607\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003eNo.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003esex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003eAge\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003eOnset\u003c/p\u003e\n \u003cp\u003eAge\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\"\u003e\n \u003cp\u003eclinical manifestation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003ediagnose\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"44\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003epredisposition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003esymptom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eConcomitant disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"24\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd height=\"38\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e73y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003enervous\u003c/p\u003e\n \u003cp\u003etired\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eabdominal spasms, spasms of both lower limbs,\u003c/p\u003e\n \u003cp\u003estiffness and sweating\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSPS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"76\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e66y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003estiff limbs and dysphagia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ehypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSPS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"76\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e45y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003estiffness and spasms in the right lower extremity\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDM;\u003c/p\u003e\n \u003cp\u003ethyroid dysfunction;\u003c/p\u003e\n \u003cp\u003enRNP/Sm(+);\u003c/p\u003e\n \u003cp\u003eANA: 1:100(+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSPS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"76\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e64y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e61y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003enight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ethrobbing pain, cramp and stiffness in both lower limbs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDM;\u003c/p\u003e\n \u003cp\u003eVitiligo;\u003c/p\u003e\n \u003cp\u003ethyroid dysfunction;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;SSA(60)+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSPS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"76\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e21y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e15y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003emenstruation\u003c/p\u003e\n \u003cp\u003enervous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003einawareness, limbs twitching and memory loss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ehashimoto\u0026apos;s thyroiditis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eLE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"76\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e34y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e32y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003edizziness, limb numbness and olfactory hallucinations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDM;\u003c/p\u003e\n \u003cp\u003eANA: 1:100(+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eAE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"76\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e71y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e71y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003estiff limbs and dyspnea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ethymoma (type B1);\u003c/p\u003e\n \u003cp\u003ecervical carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSPS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"76\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e41y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e31y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003enervous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ediplopia, stiff limbs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSCH;\u003c/p\u003e\n \u003cp\u003eANA 1:320(+);\u003c/p\u003e\n \u003cp\u003eACA IgM(+)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSPS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"76\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003epoor awareness, twitching of limbs and memory loss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSSA(60)+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eLE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"76\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eburping, nausea, and vomiting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ethymic hyperplasia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eAE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"76\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eAbbreviations: M: male; F: female; SPS: stiff-person syndrome; LE: limbic encephalitis; AE: autoimmune encephalitis; ANA: anti-nuclear antibody; DM: diabetes mellitus; SCH: subclinical hypothyroidism; ACA: anticardiolipin antibody\u003c/p\u003e\n \u003cdiv\u003e\n \u003cp\u003e\u003cstrong\u003e2.2 Auxiliary inspection\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e2.12 Laboratory examination\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Blood GAD antibodies were tested in all 10 patients and GAD-65 was positive (the first 2 patients were treated with western blot assay (WBA) method and the titer could not be mmeasured. And the last 8 patients were treated with Cytometric Bead Array (CBA), and the GAD-65 titers were 1:100, 1:1000, 1:1000, 1:3200, 1:1000, 1:3200, 1:1000, 1:320 respectively). The ratio of neutrophil/lymphocyte ranged from 1.35 to 9.75; there were 4 cases with hemoglobin lower than normal, and they were anemia of different degrees, all of which were iron deficiency anemia; all the platelets were normal; only 1 case had a mild increase in C-reactive protein; there were 2 cases of elevated erythrocyte sedimentation rate, and both patients were negative for autoimmune antibodies; there were 2 cases of elevated immunoglobulin G, one of which was 1:320 positive for antinuclear antibody, and positive for anticardiolipin antibody IgM, but both cases were normal for immunoglobulin A; the immunoglobulin M was elevated in 1 case with nRNP/Sm positive in ENA and antinuclear antibody 1:100 positive in ANA; the immunoglobulin IgE was increased in 2 cases; complement C3 was decreased in 7 cases; complement C4 was all normal; the serum glutamyl transpeptidase was elevated in 4 cases; ceruloplasmin was decreased in 5 cases; hepatitis B antibody was positive in 7 cases; transferrin was reduced in 7 cases; vitamin B6 was reduced in 7 cases; total cholesterol and triglycerides were increased in an older patient, LDL was all normal; blood potassium and blood sodium were all normal; blood calcium was decreased in 1 older patient; glycosylaed hemoglobin was increased in 1 older patient; 4 patients were positive for thyroid antibodies; 9 were positive for fecal transferrin, which may be related to hormonal therapy; 1 case was positive for nRNP/Sm, 1:100 positive for antinuclear antibody; 2 cases were positive for SSA (60); 1 case was 1:320 positive for antinuclear antibody,and was positive for anticardiolipin antibody IgM ; 1 case was 1:100 positive for anti-nuclear antibody nuclear granular type; blood homocysteine was all normal; the D-dimers were all normal; .\u003c/p\u003e\n \u003cp\u003eCSF Results: there were 8 patients who underwent lumbar puncture, 5 patients sent cerebrospinal fluid GAD antibodies, and the GAD65 in CSF of 5 patients was positive, and the titers were 1:100,1:320,1:100,1:32 and 1:32 respectively, among which patient 6\u0026rsquo;s GAD65 1:100 (+) was combined with GAD67 1:30 (+); 4 patients were sent for paratumor antibody and autoimmune encephalitis antibody tests at the same time, and the results were all negative.\u0026nbsp;The number of CSF cells ranged from 0 to 6, sugar cells ranged from 2.88 to 7.2, and protein ranged from 0.12 to 0.38 in 5 patients, indicating that the cerebrospinal fluid routine and biochemistry were normal or mildly altered.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e2.2.2 Electroencephalogram and electromyography examination\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eAll 10 patients had EEG examination in the acute stage. Among them, 2 patients had mildly abnormal EEG, and the frontal and whole brain were scattered in theta band power enhancement with no epileptiform discharge. All 6 patients diagnosed with stiff-person syndrome underwent EMG examination, and the characteristic changes of continuous muscle motor unit electrical activity (CMUA) were seen in the group of muscles at rest. 1 case was combined with positive superficial peroneal sensation in the right lower limb, positive median sensation in both upper limbs, and 1 case was suggestive of cerocacral abnormality, and positive ulnar nerve sensation in the left side.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e2.2.3 radiographic examination\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eAll 10 cases had head magnetic resonance imaging (MRI), among which the 5\u003csup\u003eth\u003c/sup\u003e, 6\u003csup\u003eth\u003c/sup\u003e and 9\u003csup\u003eth\u003c/sup\u003e cases underwent cranial TSPO, PRT-CT and/or FDG-PET examinations: one case had uneven and slightly elevated TSPO distribution on the medial temporal lobe on both sides, and the left side was obvious; one case had high metabolism of the left amygdala and left hippocampus on PET-CT; FDG metabolism in one case decreased on the medial frontal lobe of both sides. Whole-body PET-CT was performed in the 8\u003csup\u003eth\u003c/sup\u003e patinet and no obvious abnormalities were found. Cranial MRI or PETT-CT examination indicated that there were 3 cases of abnormal signals in the hippocampus or temporal lobe, as shown in Table 2.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e3.2 Follow-up visits and results\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e9 out of 10 patients received immunotherapy (the first case only received symptomatic treatment: clidazepam, baclofen, immunotherapy was refused, so he died six months later, and he was also the oldest, indicating that the elderly do not recover well without timely diagnosis and treatment,and early immunotherapy is crucial), among which 3 cases were treated with first-line treatment alone (the 2\u003csup\u003eth\u003c/sup\u003e and 10\u003csup\u003eth\u003c/sup\u003e case: r-globulin, the 4\u003csup\u003eth\u003c/sup\u003e and 9\u003csup\u003eth\u003c/sup\u003e case: methylprednisolone, r-globulin, plasma exchange), and the 5\u003csup\u003eth\u003c/sup\u003e case of first-line combined with second-line treatment (the 3\u003csup\u003eth\u003c/sup\u003e case: methylprednisolone, r-globulin and mycophenolate mofetil; the 5\u003csup\u003eth\u003c/sup\u003e case: methylprednisolone, ketotezomib and cyclophosphamide; the 6\u003csup\u003eth\u003c/sup\u003e case: methylprednisolone, r-globulin, azathioprine; the 7\u003csup\u003eth\u003c/sup\u003e case: methylprednisolone, r-globulin and Ofa tolimab; the 8\u003csup\u003eth\u003c/sup\u003e case: methylprednisolone, \u0026nbsp;r-globulin and mycophenolate mofetil). Four cases received antiepileptic drugs, and three of them required a combination of two or more antiepileptic drugs. Ten patients were followed up, one died half a year later, the other 9 had improved symptoms (mRS score≧1 point), and one left right ankle and foot deformities, as detailed in Table 2.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2 Examinations and treatments of 10 patients with serum GAD 65\u003c/strong\u003e\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"609\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003eNO.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003eAntibody titer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003eAccessory examination\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003eTreatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003eOutcome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"44\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd height=\"21\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eblood\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCSF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"26\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGAD65 (BLOT): Positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCranial MRI (-).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCZP; BCF.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003edie\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGAD65 (BLOT): Positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCranial MRI \u0026nbsp;(-).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eIVIG.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eturn better\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGAD65(CBA) 1:100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCranial MRI \u0026nbsp;(-).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMPPT;\u003c/p\u003e\n \u003cp\u003eIVIG; MMF.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eturn better\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGAD65 (CBA) 1:1000 +\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCranial MRI (-).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMPPT;\u003c/p\u003e\n \u003cp\u003eIVIG; PE.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003epartial remission, leaving right ankle and foot deformity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGAD65 (CBA) 1:1000 +\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;Cranial MRI (-);\u003c/p\u003e\n \u003cp\u003euneven and slightly elevated TSPO in bilateral medial temporal lobes.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMPPT, ketotezomib; RTX.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eturn better\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"145\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGAD65 (CBA) 1:1000 +\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGAD65 (CBA)：1:100+；\u0026nbsp;GAD67 (CBA) 1:30+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCranial MRI and PET-CT showed abnormalities in left temporal pole and hippocampus;\u003c/p\u003e\n \u003cp\u003eAbnormal EEG.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMPPT; IVIG;\u003c/p\u003e\n \u003cp\u003eAZP.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eturn better\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGAD65 (CBA) 1:3200 +\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGAD65 (CBA)：1:320+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCranial MRI (-);\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMPPT; IVIG; kesimpta.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eturn better\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGAD65 (CBA) 1:3200 +\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGAD65 (CBA)：1:100+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCranial MRI (-);\u003c/p\u003e\n \u003cp\u003ePET-CT (-).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMPPT; IVIG; MMF.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eturn better\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGAD65 (CBA) 1:1000 +\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGAD65 (CBA)：1:32+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCranial MRI (-);\u003c/p\u003e\n \u003cp\u003eFDG metabolism of bilateral medial frontal decreased.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMPPT; IVIG;\u003c/p\u003e\n \u003cp\u003ePE.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eturn better\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGAD65 (CBA) 1:320\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGAD65 (CBA)：1:32+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCranial MRI (-).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eIVIG.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eturn better\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eNote: CSF: Cerebrospinal fluid; WBA: Western blot assay; CBA: Cytometric Bead Array; ND: Not done; MRI: magnetic resonance imaging; PET-CT: Positron Emission Tomography-Computed Tomography; FDG: fluorodeoxyglucose; EEG: electroencephalo-graph; CZP: clonazepam; BCF: baclofen; IVIG: Intravenous immunoglobulin; MPPT: Methylprednisolne pluse therapy; MMF: Mycophenolate Mofetil; PE: plasma exchange; RTX: rituximab; AZP: azathioprim; \u0026nbsp; (-): no significant abnormalities.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv\u003e\u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u0026nbsp;Glutamic acid decarboxylase (GAD), first reported in the New England Journal of Medicine in 1988, is a rate-limiting enzyme in the formation of \u0026gamma; -aminobutyric acid (GABA)\u003csup\u003e7\u003c/sup\u003e. GAD antibodies can block GABA synthesis either by inhibiting GAD enzymatic activity or by blocking GAD 65-mediated vesicle trafficking\u003csup\u003e1\u003c/sup\u003e, which has been implicated in a variety of neurological syndromes, including SPS, CA, LE, palatine myoclonus, nystagmus, epilepsy and so on, which can occur simultaneously with one or more conditions\u003csup\u003e8\u003c/sup\u003e. Of the 8 patients in this study, 6 cases were SPS, 1 case was LE with seizures, 1 case was LE with C, and 1 case was autoimmune encephalitis with brainstem cerebellia. GAD antibody configurations include GAD65 and GAD67, which are respectively encoded by different chromosomal genes, and have 71% homology in the C-terminal domain and cofactor-binding region\u003csup\u003e9\u003c/sup\u003e. GAD 65 is mainly distributed on synaptic vesicles, mediating the transient synthesis of GABA under acute demand stress and promoting the transfer of synaptic vesicles to synaptic terminals\u003csup\u003e10\u003c/sup\u003e. The detection of GAD67 in peripheral blood or CSF depends on the presence of GAD65 antibody. It does not exist alone and its titer is often lower than that of GAD65, and it is usually not pathogenic\u003csup\u003e11\u003c/sup\u003e. In this paper, case 6 had a 1:100 (+) GAD65 antibody in the cerebrospinal fluid and a 1:30 positive GAD67 antibody was detected, and GAD65 was considered responsible for the disease.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;GAD65-positive autoimmune nervous system disease is more common in women, which can occur at different ages and are mostly subacute with prodromal symptoms such as headache, fever, dizziness, diplopia, etc. Clinical manifestations can include seizures, cognitive decline, mental and behavioral abnormalities, ataxia, dysarthria, movement disorders, involuntary movements and decreased level of consciousness, etc\u003csup\u003e12-14\u003c/sup\u003e. In this article, the male-to-female ratio of 10 patients was 1:9, among which 2 cases could be triggered by mental tension or menstrual period, 1 case with muscle spasm was more obvious at night, and 2 cases with precursor symptoms such as dizziness and diplopia. Clinical manifestations include: spasm of both lower limbs, laryngeal muscle spasm, abdominal spasm, epilepsy with memory loss, olfactory hallucinations, dizziness, hiccup with diplopia, etc.\u003c/p\u003e\n\u003cp\u003eBrain MRI is one of the most commonly used detection techniques for diagnosing GAD65-positive autoimmune neurological disease, and some literature has pointed out that brain MRI is slightly different in the different courses of GAD 65 related encephalopathy, and in some cases, there is no obvious abnormality in the early stage of brain MRI, and in some patients, one or more intracranial lesions can be seen on brain MRI, especially in the limbic system\u003csup\u003e15\u003c/sup\u003e. In addition, with the development of imaging techniques, TSPO, FDG-PET and other examinations have been successively used in the diagnosis of neurological disease\u003csup\u003e16-18\u003c/sup\u003e. All 10 patients had head magnetic resonance (MRI), and 1 case had abnormal signals in the hippocampus or temporal lobe. Among them, case 5 was examined by cranial TSPO and FDG-PET, and the distribution of TSPO in both medial frontal lobes was uneven and slightly increased, which was obvious on the left side; the bilateral medial frontal FDG metabolism was decreased. Case 8 underwent a systemic PET-CT, with no obvious abnormalities. It is suggested that imaging examinations such as MRI, TAPO and FDG-PET have certain diagnostic significance for GAD65-positive autoimmune neurological diseases.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Similar to the literature\u003csup\u003e8\u003c/sup\u003e, the cell number and protein in CSF of 8 patients were essentially normal with positive intrathecal synthesis of anti-GAD65 antibody. The most of the EEG tests were normal, 2 cases were mildly abnormal, and the frontal and whole-brain were scattered in the theta band power enhancement, and no epileptiform discharges were found. The literature has pointed out that some patients may also have unilateral or bilateral diffuse slow waves and sharp slow waves in the frontotemporal areas on EEG, which has certain suggestive significance for diagnosis. The diagnosis of GAD-65 disease mainly depends on the detection of CSF and serum GAD antibody. In this paper, serum GAD-65 antibody was all positive, the results of CSF GAD65 antibody were all positive in 5 cases, and the positive rate of CSF was \u0026nbsp;lower than that of seroprevalenc\u003csup\u003e19,20\u003c/sup\u003e。\u003c/p\u003e\n\u003cp\u003eAnti-GAD65 antibodies are a biological marker of autoimmunity in central nervous system and non-neurological diseases. GAD65 is common in non-neurological autoimmune diseases, including type 1 diabetes, autoimmune thyroid disease and pernicious anemia. Thyroiditis is common, usually with a personal or family history of autoimmunity\u003csup\u003e21,22\u003c/sup\u003e. In addition to GAD65 pathogenic antibodies, it can coexist with other kinds of autoantibodies, such as anti-NMDAR, anti-GABAA, anti-LGI1DR, as well as paraneoplastic antibodies, while positive \u0026nbsp;multiple anti-neuronal antibodies can lead to changes or superposition of clinical symptom\u003csup\u003e21,22\u003c/sup\u003e. In addition to GAD65 pathogenic antibodies, it can coexist with other kinds of autoantibodies, such as anti-NMDAR, anti-GABAA, anti-LGI1DR, as well as paraneoplastic antibodies, while positive \u0026nbsp;multiple anti-neuronal antibodies can lead to changes or superposition of clinical symptoms\u003csup\u003e18,24,25\u003c/sup\u003e. Therefore, to establish the pathogenic link between GAD65 antibody and disease, it is necessary to exclude the influence of other antibody. Graus scholars pointed out that firstly, there is a high level of GAD65 antibody in serum, and secondly, GAD65 antibody is also present in cerebrospinal fluid, and it needs to be proven that the antibody is synthesized intrathecally\u003csup\u003e26\u003c/sup\u003e. In seven patients, high titers of GAD65 antibodies were present in both serum and cerebrospinal fluid , supporting the pathogenicity of GAD65 antibodies; 3 patients with complicated diabetes mellitus, 3 patients with positive thyroid antibodies (thyroglobulin antibodies, anti-thyroid myeloperoxidase), 4 patients with different degrees of anemia (hemoglobin minimum 83), 5 patients with positive autoimmune antibodies (2 cases with positive SSA antibodies , 1 case was 1:100 positive for anti-nuclear antibody nuclear granular type, 1 case was 1:100 positive for anti-nuclear antibody and nRNP / Sm, and 1 case was 1:320 positive for anti-nuclear antibody and anti-cardiolipin antibody IgM).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Although the autoimmune nature of GAD65 antibodies is usually non-neoplastic, the possibility of cancer cannot be completely ruled out, especially in people at high risk of cancer, such as those with a family history of cancer or a high suspicion of cancer. It has been noted in the literature that GAD65 associated stiff-person syndrome can be accompanied by a variety of cancers such as small cell lung cancer and breast cancer\u003csup\u003e27\u003c/sup\u003e, and it has also been reported to be combined with thymic tumors,and its symptoms can be completely resolved after thymectomy (complex autoimmune disorder [J].J NeurolNeurosurg Psychiatry, 2015,86(8):840-848.）.Studies have identified GAD as the main autoantigens of type 1 diabetes, and it can also be ectopically transcribed and expressed in specific cell populations of the thymus\u003csup\u003e28\u003c/sup\u003e, Thymic dysfunction can play an important role in the development of type 1 diabetes\u003csup\u003e29\u003c/sup\u003e; Additional studies pointed out that GAD65 can also promote the expression of inflammatory cytokines IFN- \u0026gamma; and IL-10 mRNA in vitro cultured thymocytes, suggesting that the GAD 65 antibodies are closely related to the thymus\u003csup\u003e30\u003c/sup\u003e. In this paper, one patient had two thymic and pleural metastasis surgeries, and the postoperative pathology was thymoma (type B1), and one patient had thymic hyperplasia. Both patients underwent thymectomy, and the symptoms were completely relieved after surgery. It suggests that thymic dysfunction may play a role in GAD65 antibody-positive autoimmune neurological disease, and surgical resection of the tumor may benefit in patients with GAD65 antibody disease with thymic hyperplasia or tumors.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The pathogenicity of GAD antibodies remains controversial, and some studies indicate that GAD antibodies are mainly through T cell-mediated immune response indicators\u003csup\u003e31\u003c/sup\u003e. In contrast, a small number of studies have confirmed that intrathecal injection of GAD antibodies in patients with SPS or CA is sufficient to reproduce typical disease manifestations in animal models, supporting the hypothesis that GAD-Ab may exhibit a direct pathogenic mechanism\u003csup\u003e32,33\u003c/sup\u003e. Further studies have found that CSF GAD65-Abs can cross-react with muscle cell membranes, suggesting that GAD65-Abs may directly bind to receptors on muscle cell membranes in the same way as antigen-antibody reactions, thus playing an important role in muscle movement regulation\u003csup\u003e34\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe treatment of GAD65 antibody-positive autoimmune neurological diseases is still dominated by immunotherapy, including high-dose intravenous prednisolone pulse, intravenous immunoglobulin (IVIG) injection, and plasmapheresis in the acute phase, and the recovery period includes oral methylprednisolone, immunosuppressants, and rituximab to prevent recurrence in the convalescent phase\u003csup\u003e35\u003c/sup\u003e. Clinical experience shows that initiating immunotherapy as soon as possible in the early stage of the disease is crucial for good recovery, and patients who do not accept immunotherapy have poor outcomes. The 1th Patient died half a year after receiving no immunotherapy, and the last 9 patients started immunotherapy immediately after diagnosis, except for the 4\u003csup\u003eth\u003c/sup\u003e patient who had a long course of disease, older age, and more underlying diseases, and limited improvement in clinical symptoms after immunotherapy, leaving right ankle and foot deformities, the remaining 8 cases were significantly improved.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e\u0026nbsp;Anti-GAD65 antibody encephalitis is more common in young and middle-aged people, more women than men, and the clinical manifestations mainly include SPS, LE, AE, etc., and single or multiple symptoms exist at the same time. High titer of GAD65 antibody in serum is the gold standard for diagnosis. As epilepsy is often difficult to control, immunotherapy has a good effect on the vast majority of patients. Early diagnosis and prompt initiation of immunotherapy are essential to improve clinical symptoms and reduce recurrence and permanent disability. Therefore, attention should be paid to timely diagnosis and the implementation of appropriate treatment to obtain a better recovery for patients.\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e \u003cstrong\u003eassistance\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Scientific Project of NO 905 Hospital of PLA Naval (2021 X003), the Zhuyuan Scientific Project of the Nursing School of Naval Medical University (2022KYZ09), the Outstanding Young Talents Training Project of Naval Medical Center (21TPQN2701) and the \u0026quot;Qiang-Ji\u0026quot; project of Naval Medical Center (23M2701).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients or their next of kin provided informed consent for inclusion in the case series\u0026nbsp;and the aims of the study completely explained.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have no conflicts of interest to report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYJW, MMW and KLJ: Investigation, Conceptualization, Writing-Original Draft, Writing-Review and Editing. LYG, MLW and YC: Investigation, Writing-Original Draft. JW and YH: Investigation, Supervision, Project administration and Editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMcKeon A, Tracy JJM, nerve. GAD65 neurological autoimmunity.2017;56(1):15-27.\u003c/li\u003e\n\u003cli\u003eDalakas M, Yi JJTaind. Late-onset stiff-person syndrome: challenges in diagnosis and management.2023;16:17562864231214315.\u003c/li\u003e\n\u003cli\u003eKaaden T, Madlener M, Angstwurm K, et al.Seizure Semiology in Antibody-Associated Autoimmune Encephalitis.2022;9(6).\u003c/li\u003e\n\u003cli\u003eBauer T, David B, Ernst L, et al.Structural network topology in limbic encephalitis is associated with amygdala enlargement, memory performance and serostatus.2020;61(10):e140-e145.\u003c/li\u003e\n\u003cli\u003eForbes E, Prain K, Wong R, Gillis DJP. 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Human Stiff person syndrome IgG-containing high-titer anti-GAD65 autoantibodies induce motor dysfunction in rats.2013;239:202-209.\u003c/li\u003e\n\u003cli\u003eAli F, Rowley M, Jayakrishnan B, Teuber S, Gershwin M, Mackay IJJoa. Stiff-person syndrome (SPS) and anti-GAD-related CNS degenerations: protean additions to the autoimmune central neuropathies.2011;37(2):79-87.\u003c/li\u003e\n\u003cli\u003eZhang H, Yue J, Lian C, Long Y, He DJFii. Case Report: Extraocular muscles paralysis associated with GAD65 antibody: a case series study.2023;14:1256089.\u003c/li\u003e\n\u003cli\u003eAmaia, Mu\u0026ntilde;oz-Lopetegi, Marienke AAM, de Bruijn, et al. Neurologic syndromes related to anti-GAD65: Clinical and serologic response to treatment[J]. Neurol Neuroimmunol Neuroinflamm, 2020, 7: 0.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"glutamic acid decarboxylase 65, stiff-person syndrome, limbic encephalitis, autoimmune encephalitis","lastPublishedDoi":"10.21203/rs.3.rs-5351211/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5351211/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo study the clinical characteristics of patients with anti-glutamic acid decarboxylase-65 (GAD-65) antibody-positive autoimmune neurological diseases.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e The clinical data of 10 patients with anti-GAD-65 antibody-positive autoimmune neurological diseases who were admitted to the department of neurology of NO. 905 Hospital of PLA Navy from November 2014 to November 2023 was retrospectively analyzed.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e The age of onset of 10 patients was 15 to 72 (44.9 ± 21) years old and the confirmed age was 21 to 73 (47.3 ± 20.1) years old. The ratio of male to female was 1:9. In three cases, symptoms were easily triggered by mental stress, fatigue and around the time of menstruation, and in one case, symptoms of muscle spasms were obvious at night. Clinical manifestations: 3 cases of single or double lower limb spasm with or without abdominal cramps, 3 cases of limb stiffness with swallowing or dyspnea or diplopia, 2 cases of unconsciousness, limb convulsions with memory loss, 1 case of dizziness, limb numbness and olfactory hallucinations, and 1 case of hiccups, nausea and vomiting. The final diagnosis was as follows: 6 cases of stiff-person syndrome (SPS), 2 cases of limbic encephalitis (LE) with seizures, 1 case of autoimmune encephalitis with cerebellar ataxia (CA), and 1 case of autoimmune brainstem cerebellum. In the auxiliary examination, 10 patients were positive for different titers of GAD65 in blood and/or cerebrospinal fluid (CSF), including 1 with GAD67 positive in CSF at the same time; 5 with abnormal blood autoimmune antibodies, 4 with abnormal thyroid function, 3 had diabetes and 2 with thymoma or thymic hyperplasia. Imagological examinations of the brain indicated that 3 patients had abnormal signals in hippocampus or temporal lobe; 2 had mild abnormal electroencephalogram (EEG) with no epileptiform discharge. In 6 cases, electromyography (EMG) showed continuous muscle motor unit electrical activity in the group of muscles at rest. 1 case had positive peroneal sensation in the right lower limbs, and 1 case showed cervicofacial abnormality and left ulnar nerve sensory positive.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatments\u003c/strong\u003e Except for the first patient who only received symptomatic treatment, the remaining 9 patients were immunoreacted. Among them, 3 patients were treated with first-line treatment alone, 6 patients received first-line combined with second-line treatment, and 4 patients with seizures were treated with antiepileptic drugs. Ten patients were followed up, one died half a year later, and the remaining nine had symptoms improved (mRS score ≧ 1 point). \u003cstrong\u003eConclusion\u003c/strong\u003e Anti-GAD65 antibody encephalitis is more common in young and middle-aged people, more women than men. Its clinical manifestations mainly include SPS, CA, LE and so on. Given that single or multiple symptoms exist at the same time, high titer of GAD65 antibody in serum is the gold standard for diagnosis. Though epilepsy is often difficult to control, immunotherapy has a good effect on the vast majority of patients, and it should be started as soon as possible, which helps to improve the recovery.\u003c/p\u003e","manuscriptTitle":"Analysis of the clinical characteristics of 10 cases of serum anti-glutamic acid decarboxylase-65 antibody-positive autoimmune neurological diseases","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-27 17:28:49","doi":"10.21203/rs.3.rs-5351211/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ac5d041c-fdb2-466e-861a-a8e3c7f82f79","owner":[],"postedDate":"November 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-11-27T17:28:51+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-27 17:28:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5351211","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5351211","identity":"rs-5351211","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}