Clinical Heterogeneity in Acute Symptomatic Seizures due to Autoimmune Encephalitis Related to GAD65 Antibodies

<b><i>Introduction:</i></b> This study aimed to explore the diversity and clinical features of acute symptomatic seizures due to autoimmune encephalitis related to anti-glutamate decarboxylase (GAD) 65 antibodies. <b><i>Methods:</i></b> Clinical data of a series of 6 patients positive for anti-GAD65 antibodies were retrospectively analyzed. <b><i>Results:</i></b> Five of the patients were male and 1 was a female, with a median age of 44.1 years (range 18–70 years). Seizure forms were varied in 6 patients when they were admitted to the hospital: 3 cases of seizures only and 3 accompanied by other symptoms, such as mental disorder, cognitive impairment, cerebellar ataxia, and ocular movement disorder. Three patients (50%) had coexisting systemic autoimmune diseases, including diabetes mellitus, vitiligo, and hyperthyroidism. Five patients (83%) had abnormal brain MRI findings. They were all treated by immunotherapy, 5 of 6 patients improved significantly but relapsed after withdrawing methylprednisolone, and 1 patient got deteriorated. None of them were diagnosed with tumors. <b><i>Conclusions:</i></b> Clinical features of acute symptomatic seizures related to GAD65 antibodies are diverse, and early and continuous immunotherapy is necessary for patients.

Checkpoint Inhibitor-Associated Autoimmune Diabetes Mellitus: A Case Report

Introduction: Checkpoint Inhibitors have revolutionized the management in oncology by stimulating the immunological response to cancer. On the contrary, there is an increase in immune-related adverse effects affecting various systems including the endocrine. We report a unique case of new-onset diabetes with diabetic ketoacidosis (DKA) within 18 days of receiving checkpoint inhibitors for Merkel Cell Carcinoma. Clinical Case: An 86-year-old man diagnosed with locally advanced Merkel cell carcinoma underwent surgery and radiotherapy to his right face and neck. Four months later, the positron emission tomography (PET) scan was consistent with liver metastasis. Pembrolizumab, a programmed death receptor-1 (PD-1) inhibitor was initiated as next line treatment. Prior to starting pembrolizumab, his blood glucose was 92 mg/dL (60–120) with no previous history of diabetes mellitus. He presented 18 days later to the emergency room with altered mental status, polyuria, and polydipsia with a blood glucose of 980 mg/dL, anion gap of 26 mmol/L (5–15), and was managed for DKA with new-onset Diabetes Mellitus. HbA1C was 7.0% (4–5.6). He was discharged on subcutaneous insulin glargine once daily, pre-meals insulin aspart, and was referred to the endocrinology clinic. Further investigations obtained during the clinic visit demonstrated low C-peptide of &lt;0.7 ng/mL (0.8–6), glucose 76 mg/dL, positive glutamic acid decarboxylase (GAD-65) antibodies of &gt;25,000 nmol/mL (&lt;0.02), negative islet antigen-2 antibody, islet cell antibody and zinc transporter 8 antibodies. Other endocrine tests showed normal thyroid function, cortisol, and adrenocorticotrophic hormone (ACTH) levels. The patient was educated on checkpoint inhibitor-associated autoimmune diabetes and the need for a lifelong insulin regimen. Clinical Lesson: Our case highlights the immune-related adverse effect involving the endocrine system from checkpoint inhibitor therapy. In comparison to the other common endocrinopathies associated with checkpoint inhibitors, autoimmune diabetes is rare (~ 1–2% incidence) and only less than half demonstrate antibodies with a median time of 8 weeks since exposure. GAD-65 antibodies are the commonest antibody noted and our patient had a robust GAD-65 antibody of &gt;25,000 depleting C-peptide within 18 days of receiving the Pembrolizumab resulting in DKA with a new onset of diabetes. We conclude that diabetes mellitus is a rare but serious adverse effect of immune checkpoint inhibitor therapy. Society for Immunotherapy of Cancer Toxicity Management Working Group consensus recommendations from 2017 recommends routine screening to include baseline HbA1c, basic metabolic panel, thyroid function test, AM cortisol, and ACTH prior to treatment. It also recommends repeating the thyroid function test and basic metabolic panel to allow the monitoring of glycemic trends before each cycle.

Rare presentation of anti-GAD-65 antibody-positive autoimmune encephalitis and simultaneous onset of type 1 diabetes mellitus in a paediatric patient

A 16-year-old female patient presented with subacute onset of headaches, changes in acute mental status, expressive aphasia and auditory hallucinations. New oedema and enhancement of the temporal lobe were seen on brain MRI, with correlating subclinical seizures seen on electroencephalogram. Simultaneously, our patient was diagnosed with new-onset type 1 diabetes mellitus, with positive anti-glutamic acid decarboxylase (anti-GAD-65) antibodies in the serum. Cerebrospinal fluid studies remained negative, including anti-GAD-65 antibodies. Clinical remission was achieved with corticosteroids and intravenous immunoglobulins.

Gad-Awful Spasms

Stiff person syndrome (SPS) is a rare autoimmune neurological disease that causes progressive, fluctuating, painful muscle rigidity and spasms, generally beginning in the axial muscles, truncal region, and progressing to proximal musculature. A hyperlordotic posture is considered an early clinical hallmark of the condition. The most common pathological correlate is with anti-glutamic acid decarboxylase (GAD) 65 antibodies, but several other associated antibodies have been identified There is a clinical spectrum of disease with variants including stiff leg syndrome, progressive encephalomyelitis with rigidity and myoclonus (PERM), and a paraneoplastic variant, often associated with anti-amphiphysin antibodies. Electromyographic findings reveal continuous motor activity. Treatment modalities for SPS focus primarily on symptomatic relief to improve quality of life. Gamma amino butyric acid (GABA)ergic agonists, including benzodiazepines, such as diazepam and baclofen, are first-line therapies for muscle rigidity and spasms. Immunotherapies such as corticosteroids, intravenous immunoglobulin (IVIg), plasmapheresis, and rituximab have demonstrated benefit, As symptoms can be provoked by anxiety and emotional stressors, psychological support with cognitive behavioral therapy should be considered.