Anti-glutamic Acid Decarboxylase Research Articles

Antiglutamic Acid Decarboxylase 65 (GAD 65) Antibody-Associated Encephalitis Characterized with Choreo-dystonic Movements, Responsive to Steroid: A Case Report

Antiglutamic Acid Decarboxylase 65 (GAD 65) Antibody-Associated Encephalitis Characterized with Choreo-dystonic Movements, Responsive to Steroid: A Case Report

Not All Functional: Two Cases Highlighting the Role of Anti-Glutamic Acid Decarboxylase Antibody (GAD) 65 Antibodies in Patients Presenting with Symptoms Localizing to the CNS

Not All Functional: Two Cases Highlighting the Role of Anti-Glutamic Acid Decarboxylase Antibody (GAD) 65 Antibodies in Patients Presenting with Symptoms Localizing to the CNS

6674 Non-Progressive Diabetes Leading to Neurologic Diagnosis

Abstract Disclosure: F.L. Thelmo: None. M. Murugesh: None. B. Simon: None. Introduction: The autoantibody GAD (anti-glutamic acid decarboxylase) is highly associated with Type 1 diabetes (T1DM) and Latent Autoimmune Diabetes in Adulthood (LADA). If GAD is detected before the onset of overt diabetes, typically 80% of patients with abnormal glucose tolerance progress to insulin deficiency and the need for insulin treatment after 5 years.[1] Stiff Person Syndrome (SPS) is also associated with GAD antibodies, but in SPS, the GAD antibodies are believed to be different epitopes that target GABA production in neuromuscular pathways. We present a case of presumed LADA that did not progress for 30 years, with progressive neurologic symptoms leading to a diagnosis of SPS in later adulthood.Case: A 52-year-old female presented for evaluation of T1DM and worsening neuropathies. She had a long history of prediabetes, with mildly elevated glucose values noted on labs since her early twenties. There was no family history of T1DM or autoimmune conditions. Six years ago, she sought endocrine evaluation. HgbA1c values were 6.1 to 6.6%. Intermittent use of continuous glucose monitoring (CGM) revealed post-prandial hyperglycemia up to 180mg/dL, occasionally (but rarely) exceeding 200mg/dL. She recalls being told that she had positive antibodies (unclear which ones tested) and given a diagnosis of T1DM. She declined insulin and maintained glycemic control with carbohydrate restriction and exercise; there were no episodes of diabetic ketoacidosis. She then developed neurologic symptoms: fullness, tightness and bloating in the abdomen (diagnosed with gastroparesis on scanning) and after a COVID 19 booster in 2021, muscle spasms in the legs and back with worsening abdominal tightness. At the time of her current presentation, A1C was 6.4%, glycated albumin was 14.4% (prediabetes range 13.6 - 15.5%) and CGM time in range was 99%. A non-fasting C-peptide was 3.6 ng/mL (1.1- 4.4ng/mL) with glucose of 119 mg/dL. Repeat antibody testing revealed undetectable IA-2 and ZnT8 antibodies, but GAD was grossly elevated at 1,015.3 U/mL. Given the unusually high GAD titer, SPS was suspected, and this diagnosis was confirmed on referral to neurology. The patient was advised to liberalize diet and will be monitored with HgbA1c and serial C-peptide levels to assess progression in the future. Discussion: While high GAD antibody levels are associated with progression to insulin dependence in adults with LADA, in SPS the GAD titers tend to be even higher2. The presence of only one auto-antibody for T1DM (and not multiple), long-standing non-progressive hyperglycemia, and normal C-peptide pointed away from autoimmune diabetes being the etiology for mild glucose intolerance in this patient. If neurologic symptoms are present, high GAD should prompt the evaluation for other syndromes associated with GAD antibody epitopes such as SPS. Presentation: 6/2/2024

7923 Latent Autoimmune Diabetes of Adulthood (LADA) Complicating Common Variable Immunodeficiency (CVID)

Abstract Disclosure: L. Pathak: None. M.G. Jakoby: None. Introduction: CVID is caused by defective B-lymphocyte maturation that results in immunoglobulin deficiency. Patients with CVID are predisposed to both infections and autoimmune disorders, with approximately 20% experiencing at least one autoimmune complication. We present a patient with LADA complicating CVID. Case A 31-year-old woman was referred for newly diagnosed diabetes mellitus (DM). Medical history was notable for primary hypothyroidism and apparent chronic lymphocytic thyroiditis. A presumptive diagnosis of type 2 DM was made due to obesity, and the patient was treated with metformin. However, she could not tolerate the medication due to diarrhea. Semaglutide was substituted and tolerated without adverse effects. During the first six months of treatment with semaglutide 0.5 mg weekly, HbA1c improved from 6.4 to 5.6%. However, in the next six months, HbA1c increased to 6.6% despite full compliance with medication and stable weight. Anti-glutamic acid decarboxylase (GADA) titer was unequivocally elevated at 69.8 IU/mL (0.0-5.0), though anti-insulin and islet antigen-2 (IA-2) antibodies were undetectable. Insulin glargine was added to the patient’s diabetes regimen, and HbA1c improved to 5.5% three months later. Discussion This patient meets Immunology of Diabetes Society diagnostic criteria for LADA, namely diabetes diagnosed in adulthood (≥ 30 y), elevated diabetes-associated autoantibody titer, and insulin independence for at least six months after diagnosis. Patients with high-titer GADA tend to be younger and have more rapid and significant loss of β-cell function than patients with low GADA titers, and this patient’s rapidly waning glycemic response to semaglutide conforms with this observation. Until recently, autoimmune diabetes in the setting of CVID was thought to be an unusual complication, though the prevalence of type 1 diabetes among CVID patients in the European Society for Immunodeficiency registry is 1.6%, approximately four-fold higher than the general European population. LADA shares genetic features linked to childhood-onset type 1 DM, making it possible or evenly likely that LADA has occurred in cases of CVID, though a careful search of PubMed failed to identify reported cases. This patient illustrates the importance of considering LADA in CVID, particularly with abrupt loss of glycemic response to noninsulin therapeutic agents. Presentation: 6/1/2024

7725 Could COVID-19 Be the Trigger for Type 1 Diabetes?

Abstract Disclosure: E. Ahsan: None. F.F. Foo: None. A. Ravin: None. M. Akula: None. K. Hu: None. R. Ong: None. S. Holland: None. M. Hossain: None. J. Cheng: None. Introduction: COVID-19 disrupts glucose homeostasis, which may result in hyperglycemia and new-onset diabetes mellitus. It has been hypothesized to be caused by an increased inflammatory response, increased insulin resistance, and a degree of acute viral pancreatic damage. A meta-analysis showed that the incidence of new-onset diabetes was found to be as high as 14.4% (95% CI: [5.9%-25.8%]). Here, we report a case of COVID-19-induced diabetes to spread awareness among healthcare providers and encourage early detection to prevent long-term complications. Clinical Case: A 54-year-old African American female with a past medical history of hyperlipidemia, obesity, and hypothyroidism presented to our endocrinology office for evaluation and management of diabetes mellitus (DM). She presented with symptoms of 66-pound weight loss, polydipsia, polyphagia, and polyuria. Her labs on diagnosis were significant for blood glucose of 550 mg/dl (70-100 mg/dl), hemoglobin A1c >15.5% (<5.7%), and bicarbonate 23 mmol/L (20-31 mmol/L). She started on insulin and then switched to semaglutide after six months. Her fasting glucose on the follow-up visit was 103 mg/dl, the anti-glutamic acid decarboxylase 65 (GAD-65) antibody was 8,558.9 units/ml (<5 units/ml), C peptide was 1.9 ng/ml (0.5-2ng/ml), and Islet Antigen-2 (IA-2) autoantibody was <7.5 U/ml (0-7.49 U/ml). Despite positive antibodies, her C-peptide suggested enough beta-cell function, and she was switched from insulin to semaglutide. The patient was diagnosed with autoimmune diabetes, which may be from the COVID-19 infection, and was educated about regular follow-up and new medications like teplizumab that may help prevent the progression to needing insulin. Clinical Lesson: The exact mechanism of new-onset COVID-19-induced diabetes is still unknown. However, multiple risk factors are theorized to play a role in COVID-induced DM. These include defects in insulin production and glucose clearance, obesity, stress hyperglycemia, insulin resistance, and steroid therapy. Our patient had a history of obesity but no history of diabetes, steroid use, or any personal or family history of autoimmune processes. Compared to COVID-19 patients with normoglycemia or hyperglycemia, patients with preexisting diabetes and newly diagnosed diabetes experienced more severe complications, such as shock, ARDS, acute kidney injury, hypoalbuminemia, and severe COVID-19 complications. Additional research is required to investigate the various pathophysiologies and treatment options, including new medications that may prevent the disease's further progression. Diabetes caused by COVID-19 should be treated cautiously, and prompt diagnosis and care are essential to preventing further complications. Presentation: 6/3/2024

Autoantibodies in Type 1 Diabetes: prevalence and clinical profiles

Type 1 diabetes mellitus (T1D) is one of the most common chronic diseases in children and is associated with acute and serious chronic complications. T1D is characterized by the destruction of insulin-producing beta cells in the pancreas, with the emergence of circulating autoantibodies (a-Abs) targeting β cell antigens. Identifying autoantibodies can help predict the onset of T1D and associated autoimmune disorders, enhancing patient management strategies.We aimed to determine the prevalence of T1D autoantibodies and their clinical significance in the pediatric and adult populations. A multicenter cross-sectional study was carried out on 276 patient-first with T1D, including 167 pediatric (60.5%) and 109 adult (39.5%) cases, of which 144 were female and 132 were male (sex ratio = 0.91),with an average age of 14.1 ± 8.0 years. The immunological investigation was based on the detection of T1D related a-Abs, including anti-insulin, anti-glutamic acid decarboxylase (GAD65), anti-insulinoma-associated antigen 2 (IA2), and anti-zinc transporter 8 (ZnT8) specificities. The results revealed an overall autoantibody seropositivity rate of 75.36% (n = 208). Among the positive cases, GAD65 antibodies were the most prevalent at 37.31%, followed by anti-insulin and anti-ZnT8 antibodies, each at 36.59%, and anti-IA2 at 28.62%. Additionally, 45,67% of patients had one a-Abs, 28.36% had a two, 21.15% had three, and 4.8% had all four a-Abs.A statistically significant difference was observed between the seropositive and seronegative groups regarding the presence of associated autoimmune diseases (p=0.005). These findings align with the existing literature, highlighting the importance and scientific value of detecting a-Abs in patients with T1D.

A rare presentation of stiff-person syndrome with a nonspecific focal myositis: A case report

Introduction. The stiff-person syndrome (SPS) is a rare disease whose incidence is estimated at approximately 1 in a million individuals in the general population. Diagnosis relies on a combination of clinical, immunological, and electromyographic items. We present the case of a patient diagnosed with the idiopathic SPS, initially misdiagnosed as focal paravertebral myositis. Case presentation. A 36-year-old patient was referred to us for the investigation of subacute dorsal myalgias. The patient reported a severe torticollis seven months ago, which resolved spontaneously after one month, and some episodes of back stiffness. On examination, the patient was afebrile, had hyperlordosis with a paravertebral contracture and tenderness. Neurological and cognitive examinations were normal. C-reactive Protein was at 137 mg/l. The rest of laboratory investigations, including creatine phosphokinase (CPK), were within normal range. Spinal MRI revealed T2 hyperintensity in the semispinalis muscle, erector spinae muscle, trapezius muscle, as well as the intervertebral muscles. Therefore, focal paravertebral myositis was suspected. The electromyogram (EMG) revealed the presence of a continuous motor unit activity in agonist and antagonist muscles, suggestive of stiff-person syndrome. Antinuclear antibodies, anti-glutamic acid decarboxylase 65 and onconeuronal antibodies were negative. Analysis of the cerebrospinal fluid, including anti-glutamic acid decarboxylase 65 test, was normal. We noticed that the paravertebral contracture became less noticeable when the patient was commenced on diazepam. Diagnosis of SPS was established according to Dalakas criteria. Investigations for an underlying neoplasm, were normal. Associated autoimmune disorders have been ruled out. The MRI description was rather explained by the continuous contraction of the affected muscles. Treatment included diazepam, baclofen, intravenous immunoglobulin and corticosteroids. The patient showed important signs of improvement. Conclusion. SPS is a rare condition whose diagnosis can be delayed. Recognizing and managing SPS as early as possible is crucial. It is based on clinical reasoning, imaging, biological features and EMG.

Pediatric Case of Autoimmune Cerebellitis with Positive Anti-GAD Antibodies and Accidental Finding of Roth Spots

Abstract We present a pediatric case of autoimmune cerebellitis, which was distinguished by the presence of positive anti-glutamic acid decarboxylase (anti-GAD) antibodies. The patient, a young child, presented with a four-day history of progressively worsening headaches, coupled with persistent vomiting. These symptoms prompted immediate medical evaluation. Initial computed tomography (CT) imaging revealed a hypodense area in the left cerebellum and mild hydrocephalus, indicating fluid accumulation in the brain. Subsequent magnetic resonance imaging (MRI) provided more detailed visualization, confirming the diagnosis of acute cerebellitis, which was characterized by bilateral enlargement of the cerebellum and an associated mass effect that exerted pressure on the adjacent brain structures. The medical team initiated a comprehensive treatment regimen that included antibiotics to address any potential bacterial infection, antivirals to counter possible viral etiologies, immunoglobulin therapy to modulate the immune response, and corticosteroids to reduce inflammation. The patient responded well to this treatment protocol, with follow-up imaging showing a significant reduction in cerebellar swelling and overall improvement in clinical symptoms. The detection of elevated anti-GAD antibodies, along with anti-thyroglobulin antibodies, indicated an autoimmune origin of the cerebellitis. This autoimmune response can lead to the body’s immune system mistakenly attacking healthy brain tissue. Moreover, the incidental finding of a Roth spot, a retinal hemorrhage with a white center, during a routine eye examination suggested potential systemic involvement, possibly indicating a broader immune-mediated condition.

Exploring the diverse phenotypes of anti-GAD 65 encephalitis, diagnosis and treatment challenges

Objectives. To present two cases of anti-glutamic acid decarboxylase 65 (anti-GAD65) antibody encephalitis with different clinical phenotypes. Introduction. Anti-glutamic acid decarboxylase 65 antibody encephalitis (GAD-65 AE) is a rare pathology with a high potential for severity, having multiple forms of presentation and multiple differential diagnoses. This presentation aims to exemplify the strong clinical heterogeneity that is associated with this clinical entity by putting forth two cases that were treated in our clinic, each representing a separate clinical phenotype of this pathology. Material and methods. We analyzed two cases from our clinic of autoimmune encephalitis with positive anti-GAD65 antibodies and compared the cases with the data from the literature regarding clinical presentation, differential diagnosis, treatment, and evolution. Content. The first case presented is a woman aged 71 (66 at onset) presenting with progressive cerebellar ataxia. She was diagnosed with GAD-65 AE based on clinical presentation and positive anti-GAD65 antibodies titer. She was initially treated with methylprednisolone pulse therapy and received four such courses in the first year after diagnosis, resulting in a slowing of the progression of the neurological deficit. During the COVID19 pandemic, treatment was paused and her neurological status resumed its decline, and she also developed insulin-dependent diabetes mellitus. Starting in 2021, treatment was continued, having received one course of IVIg and one course of plasma exchange in our clinic. Eventually, the treatment was switched to Mycophenolate mofetil but her status continues to decline. The second case is about a 32 years old woman, with a history of recurrent seizures and progressive memory decline that started at 28 years. She was diagnosed 11 months after the onset with limbic encephalitis with anti-GAD65 antibodies, left temporal focal epilepsy with nocturnal seizures and mild cognitive decline. She was treated with corticotherapy and IgG. She was discharged home with antiepileptic treatment with no recurring seizures, but a slow cognitive decline. She had two relapses at distance from the onset, the first one with status epilepticus and the second one with focal seizures and a generalized seizure. She developed type I diabetes with positive anti-pancreatic islet antibodies. After the first relapse, immunosuppressive therapy with Mycophenolate mofetil was initiated. The evolution was good and under immunosuppression she had only one episode of seizures in the context of a COVID-19 infection. Conclusions. Autoimmune encephalitis with positive GAD antibodies presents a very diverse clinical picture, as we can see in the presented cases.

Improved HbA1c and body weight in GADA-positive individuals treated with tirzepatide: A post hoc analysis of SURPASS.

People with clinically diagnosed type 2 diabetes (T2D) but positive anti-glutamic acid decarboxylase autoantibodies (GADA), referred to here as latent autoimmune diabetes in adults (LADA), may experience more rapid glycemic deterioration than those with T2D and may benefit from effective diabetes treatment with additional metabolic benefits. Assess glycated hemoglobin (HbA1c) and body weight (BW) changes associated with tirzepatide in GADA-positive versus GADA-negative participants with clinical T2D diagnosis. Post hoc analyses based on pooled data from SURPASS 2-5, using mixed-model repeated measures from the efficacy analysis set, adjusting for study and baseline covariates including age, sex, baseline values, body mass index (BMI), and GADA status. N/A. N = 3791. Tirzepatide (5, 10, 15 mg). Change from baseline in HbA1c at Weeks 40 (SURPASS-2, -3, -5) and 42 (SURPASS-4)by GADA status. In participants with confirmed GADA status, 3671 (96.8%) were GADA-negative and 120 (3.2%) were GADA-positive (76 [63.3%] with low and 44 [36.7%] with high GADA levels). Baseline characteristics were similar between groups, except for slightly lower BMI in GADA-positive versus GADA-negative participants (mean [SD] BMI 32.2 [6.1] versus 33.6 [6.3] kg/m2). At Week 40/42, both groups achieved robust reductions in HbA1c (-2.11% versus -2.32%) and BW (9.2 kg versus -9.6 kg) (p < 0.001, both groups). HbA1c reductions were greater in GADA-negative participants (estimated difference [95% CI]: 0.21% [0.03, 0.39]; p = 0.024) and BW reductions did not differ between groups (0.38 kg [-0.99, 1.75]; p = 0.588). In this post hoc analysis, tirzepatide was associated with substantial reductions in HbA1c and BW irrespective of GADA status in adults diagnosed with T2D, suggesting that tirzepatide may improve glycemic control in individuals with LADA.

Frequency of C-peptide and antibody levels (anti GAD, Islet cell antibodies, insulin auto antibodies) in children of Pakistan with Type-1 diabetes.

The autoimmune mechanism in T1DM causes gradual loss of pancreatic β-cell, which progresses to hyperglycemia and ultimate reliance on consistent insulin therapy. T1DM has been the commonest type of diabetes in children and this study will help in refining indulgent towards the problem and its pathophysiology in our people. The objective was to find out the prevalence of C-peptide and antibody levels (anti GAD, ICA, IAA and IA2) in children and adolescents of Pakistan with T1DM. We conducted this cross-sectional study at Department of Pediatric Endocrinology, National Institute of Child Health, Karachi between August 2019 to February 2020 and included 98 children who had T1DM for more than one month. Subjects whose GFR was <30ml/min were omitted from the study. Among those registered subjects, C-peptide, human islet cell antibody (ICA), insulin auto antibodies (IAA) and anti-glutamic acid decarboxylase were assessed. Demographical and laboratorial facts were noted on a pre-constructed proforma. There were 77(78.3%) cases who had level of C-peptide <0.8 and anti-GAD was found in 47(48%) subjects. 35(35.7%) cases found positive for IA2 .and 7(7.1%) patients had insulin auto antibodies positive while ICA was negative in total 98(100%) subjects. Children with T1 DM possessed increased levels of anti-GAD antibodies, insulin autoantibodies and anti (IA2) but islet cells antibodies were negligible in our population when checked at a point of time. C-peptide may be normal in some, but its level declines with long duration of diabetes in children.

The significance of precise diabetes diagnosis: a case of euglycemic diabetic ketoacidosis induced by the introduction of empagliflozin with simultaneous reduction of insulin dosage

Euglycemic diabetic ketoacidosis (euDKA) is a rare but severe metabolic complication of diabetes mellitus characterised by elevated anion gap metabolic acidosis despite normal or mildly elevated blood glucose levels. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have emerged as effective antidiabetic medications, yet their use is associated with an increased risk of euDKA, especially when coupled with insulin dose reduction. We present the case of a 50-year-old male with a 20-year history of diabetes mellitus, initially managed with insulin and metformin, who developed euDKA following the introduction of empagliflozin and sitagliptin alongside a reduction in insulin therapy. Despite normoglycaemia the patient exhibited symptoms of ketoacidosis, including chronic fatigue, polydipsia, and polyuria. Diagnostic workup revealed metabolic acidosis, elevated inflammatory markers, acute kidney injury and ketonuria. Subsequent specialised laboratory tests confirmed type 1 diabetes mellitus (T1DM) with the presence of anti-glutamic acid decarboxylase (anti-GAD) antibodies and the absence of C-peptide secretion. Management involved fluid therapy, intravenous insulin and glucose administration. This case underscores the diagnostic challenges of euDKA and emphasises the importance of differentiating between T1DM and T2DM, as management strategies vary significantly. Patient education on insulin therapy and injection techniques is crucial to prevent complications such as improper insulin delivery and dose reduction, which can precipitate euDKA. In conclusion, clinicians should be vigilant for euDKA in patients on SGLT2 inhibitors, particularly when insulin dose reduction is involved. Comprehensive patient education and accurate differentiation between diabetes types are essential for timely diagnosis and optimal management, thereby reducing the risk of severe complications.

Immune Ataxias: The Continuum of Latent Ataxia, Primary Ataxia and Clinical Ataxia.

The clinical category of immune-mediated cerebellar ataxias (IMCAs) is now recognized after 3 decades of clinical and experimental research. The cerebellum gathers about 60% of neurons in the brain, is enriched in numerous plasticity mechanisms, and presents a large variety of antigens at the neuroglial level: ion channels and related proteins, synaptic adhesion/organizing proteins, transmitter receptors, and glial cells. Cerebellar circuitry is especially vulnerable to immune attacks. After the loss of immune tolerance, IMCAs present in an acute or subacute manner with various combinations of a vestibulocerebellar syndrome (VCS), a cerebellar motor syndrome (CMS), and a cerebellar cognitive affective syndrome/Schmahmann's syndrome (CCAS/SS). IMCAs include gluten ataxia (GA), post-infectious cerebellitis (PIC), Miller Fisher syndrome (MFS), paraneoplastic cerebellar degeneration (PCD), opsoclonus myoclonus syndrome (OMS), anti-glutamic acid decarboxylase (anti-GAD) ataxia, and glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A). In addition, multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), Behçet disease, and collagen-vascular disorders may also present with cerebellar symptoms when lesions involve cerebellar afferences/efferences. Patients whose clinical profiles do not fit with IMCAs are now gathered in the group of primary autoimmune cerebellar ataxias (PACAs). Latent auto-immune cerebellar ataxia (LACA) refers to a clinical stage with a slow progressive course and a lack of obvious auto-immune background. At a pre-symptomatic stage, patients remain asymptomatic, whereas at the prodromal stage aspecific symptoms occur, announcing the symptomatic neuronal loss. LACA corresponds to a time-window where an intervention could lead to preservation of plasticity mechanisms. Patients may evolve from LACA to PACA and typical IMCAs, highlighting a continuum. Immune ataxias represent a model to elucidate the sequence of events leading to destruction of cerebellar neuronal reserve and develop novel strategies aiming to restore plasticity mechanisms.

Obesity and Acanthosis Nigricans as the Clinical Markers of Insulin Resistance and Type-2 Diabetes Mellitus in Young Patients; A Case Report of Two Cases

Two young girls, aged 11 and 12 years, presented with obesity and Acanthosis Nigricans. They were found to have severe insulin resistance and type-2 diabetes mellitus. Anti-glutamic acid decarboxylase and anti-islet cell antibodies were negative. Tests for hypothyroidism and Cushing’s syndrome were negative. They were managed with lifestyle modification and metformin.

Successfully treated anti-GAD limbic encephalitis in a 15-year-old diabetic boy with intravenous immunoglobulin: case report

Introduction and importance: Limbic encephalitides (LE) have symptoms and signs of new-onset seizures accompanied by cognitive impairment and signal changes in the MRI of the limbic system in the brain. Numerous antibodies against the neurons and synapses have been detected so far. Of those, antiglutamic acid decarboxylase antibody (Anti-GAD Ab) impairs the gamma amino butyric acid, one of the primary mediators that naturally prevents abnormal neuronal activity causing seizure. Case presentation: The authors have reported a case of anti-GAD Ab LE in a diabetic male adolescent who responded dramatically to intravenous immunoglobulin and reviewed all similar pediatric cases for 15 years now. Clinical discussion: The symptoms in children suffering from anti-GAD LE in three categories, systemic, psychiatric, and neurological, are heterogeneous. The most common manifestations were seizures followed by altered mental status and behavioral changes, respectively. The two main clinical scenarios described in GAD65-mediated autoimmune epilepsy are (1) an acute/subacute onset of seizures alone or seizures (including new-onset refractory status epilepticus, NORSE) accompanied by some degrees of cognitive and psychiatric manifestations, including amnesia and mesiotemporal inflammatory involvement consistent with LE and (2) epilepsy without clinical or MRI evidence of active central nervous system inflammation. Conclusion: Although rare, the neurologist should consider the potential role of anti-GAD ab-associated encephalitis in the presence of diabetes mellitus.

O-07 Lipodystrophy: A disease to be considered in diabetes clinics

Abstract Introduction Lipodystrophy syndromes are disorders with no adipose tissue. Lipodystrophy is classified based on the degree of adipose tissue deficiency, distinguishing between partial and generalized forms, and considering if it is inherited or acquired. The condition is characterized by ectopic steatosis, severe dyslipidemia, insulin resistance, and severe comorbidities including uncontrolled diabetes mellitus (DM), acute pancreatitis, hepatic cirrhosis, proteinuria, renal failure, and premature cardiovascular disease. Congenital Generalized Lipodystrophy (CGL, Berardinelli-Seip Syndrome) is inherited autosomal recessively. Four genetic mutations linked to CGL have been identified: AGPAT2, BSCL2, CAV1, and PTRF. This report describes a case of a patient with uncontrolled diabetes and other health conditions. The patient was diagnosed with CGL2 as an adult after admission to our facility. Clinical Case This case involves a 43-year-old female patient seeking help for glycemic control and menstrual cycle irregularities. She was diagnosed with DM at 24 and received care at multiple hospitals. Her mother, older brother, and three sisters were diagnosed with DM before the age of 40. Her BMI was 23.4 kg/m2. The physical examination revealed muscularly prominent lipoatrophy in the upper and lower limbs and acanthosis nigricans in the axilla. Additionally, the person had facial features resembling acromegaly, with enlarged extremities and swelling of soft tissues. Blood pressure was regulated with ramipril, hydrochlorothiazide, and amlodipine. She had used various insulin and OAD regimens in the past. Despite this, euglycemia was challenging to achieve, and she frequently needed to be hospitalized for diabetic ketoacidosis. Anti-glutamic acid decarboxylase, anti-insulin, and islet antibodies were negative. HbA1c level was 13.3% and C-peptide level was 2.5 ng/ml. Moreover, grade 3 hepatosteatosis and hypertriglyceridemia were present. Polyneuropathy and diabetic nephropathy were also identified. Acromegaly and cushing syndrome were excluded. After excluding acquired lipodystrophy syndromes, she was consulted to the genetics department for CGL. Next-gen sequencing found a homozygous missense mutation (c.666G&amp;gt;C; p.Met222Ile) in exon 5 of the BSCL2 gene. Following this result, the patient was diagnosed as CGL2. Caloric and fat restricted dietary was recommended. Fat intake was below 20-30% of total energy. The patient was treated with insulin aspart, glargine U300/mL, metformin, alpha lipoic acid, and fenofibrate. The patient's blood glucose was more regulated, did not apply to the emergency department. Family members were also given genetic counseling. Conclusion Lipodystrophy is rare however medical professionals must exercise caution and consider lipodystrophy as a possible diagnosis for non-obese individuals who have difficulty maintaining euglycemia, fatty liver disease, and elevated triglyceride levels. The physical examination is crucial for diagnosis.

Altered antibody titers in patients with neuromuscular diseases after high-dose intravenous immunoglobulin therapy

We investigated the changes in antibody titers after intravenous immunoglobulin (IVIg) administration in patients with neuromuscular diseases. Among patients who received IVIg from April 1, 2020, to August 31, 2022, we retrospectively evaluated 15 patients with antibody measurements before and after IVIg administration for any rise in the following antibody levels and examined the data for subsequent changes of false positive results to negative ones. The levels of anti SS-A, anti-thyroglobulin, anti-thyroid peroxidase, anti-glutamic acid decarboxylase, HBs, and HBc antibodies transiently increased after IVIg administration and showed false-positive results. However, levels of rheumatoid factor and anti-nuclear and antineutrophil cytoplasmic antibodies were not elevated. The false-positive results became negative after 3 months. Here, we report on the changes in antibody levels before and after IVIg administration and note that levels of hepatitis B virus-related antibodies and various autoantibodies transiently rise after IVIg administration.

Anti-glutamic acid decarboxylase antibodies-associated cerebellar ataxia: A treatable ataxia

Abstract Background: Anti-glutamate decarboxylase 65 antibody-associated cerebellar ataxia (anti-GAD65Ab-associated CA) is the most widely studied immune-mediated CA. There are few case series evaluating the clinical, radiological, treatment profile, and outcome of anti-GAD65Ab-associated CA. Objective: To study the clinical, radiological profile, associated neoplasm, treatment outcome, and prognosis in patients diagnosed with anti-GAD65Ab-associated CA. Methods: A retrospective descriptive analysis of a cohort of patients diagnosed with anti-GAD65Ab-associated CA was performed and analyzed. Results: Thirteen patients were selected for the analysis with female predominance (70%). The mean age at presentation was 47.5 ± 11.1 years (range, 29–65 years), and the median duration of the symptoms was 4 months. All 13 patients (100%) had gait ataxia. Ten patients had limb ataxia along with gait ataxia (75%). Seven patients had cerebellar dysarthria (54%). Four patients (31%) had gaze-evoked jerky nystagmus. Five patients (39%) were diagnosed with type 2 diabetes mellitus, and one patient had hypothyroidism in addition to type 2 diabetes mellitus. Brain magnetic resonance imaging was normal in seven (54%) patients, and pure cerebellar atrophy was observed in six patients. One patient was detected with a colon neoplasm. All 13 patients received intravenous methylprednisolone, followed by oral steroids over 3 months. Six patients (50%) received plasma exchange along with intravenous methylprednisolone. Favorable outcomes (modified Rankin scale score ≤2) were observed in five patients and poor outcomes in two; six patients were lost to follow-up after the first admission. Conclusion: Anti-GAD65Ab-associated CA presents as subacute to chronic progressive CA with a favorable outcome with immunotherapy. Anti-GAD antibodies should be assessed in serum or cerebrospinal fluid in patients presenting subacute to chronic sporadic CA. The occurrence of a systemic neoplasm is rare in anti-GAD65Ab-associated CA.

Autoimmune Retinopathy in a Patient with Stiff-Person Syndrome: A Case Report.

To describe a patient who developed retinal degeneration associated with autoimmune retinopathy (AIR) and who was also found to have anti-glutamic acid decarboxylase (GAD65) autoantibodies and the diagnosis of stiff-person syndrome (SPS). Ophthalmologic workup consisted of clinical examination, multi-modality retinal imaging, and electrophysiologic testing. Further neurologic assessment including relevant serum and cerebrospinal fluid studies was also conducted. We highlight the case of a 45-year-old patient who developed subacute, sequential vision loss, along with bilateral lower extremity weakness. On initial presentation, optical coherence tomography (OCT) of the left eye was notable for diffuse attenuation of the outer retinal bands. Fundus autofluorescence demonstrated a ring of hyper-autofluorescence encircling the fovea of the left eye. At fifteen-month follow-up, the right eye also became similarly affected. He was found to have elevated serum and cerebrospinal anti-GAD65 autoantibodies and was diagnosed with both SPS and AIR. There is a potential association of anti-GAD65 autoantibodies with the development of AIR.

Paraneoplastic Neurologic Syndromes.

Progress is ongoing in understanding paraneoplastic neurologic disorders, with new syndromes and antibodies being described and more detailed evidence available to guide workup for diagnosis and treatment to improve outcomes. Many excellent reviews have summarized the molecular features of different antibodies, but this article emphasizes the clinical features of each syndrome that may help guide initial diagnosis and treatment, which often should occur before an antibody or cancer is found to confirm the diagnosis. Recent findings include updated diagnostic criteria with validated sensitivity and specificity, discovery of novel antibodies, and clinical findings that increase the likelihood of an underlying paraneoplastic disorder. Suggestive syndromes that have been recently identified include faciobrachial dystonic seizures and pilomotor auras in anti-leucine-rich glioma inactivated protein 1 encephalitis, extreme delta brush on EEG in N-methyl-d-aspartate (NMDA)-receptor encephalitis, déjà vu aura in anti-glutamic acid decarboxylase 65 (GAD65) encephalitis, and sleep disturbances in several disorders. In addition, there is confirmed utility of brain positron emission tomography (PET) and CSF markers, including carcinoembryonic antigen and oligoclonal bands, as well as improved tests for the presence of leptomeningeal cancer cells in CSF. Associations of cancer immunotherapies with paraneoplastic syndromes and herpes simplex virus encephalitis (and COVID-19) with NMDA-receptor encephalitis have been described. All neurologists should be aware of advances regarding paraneoplastic neurologic syndromes, as patients can present with a wide variety of neurologic symptoms and earlier diagnosis and treatment can improve outcomes.