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Immunotherapy-Induced Glutamic Acid Decarboxylase 65 Cerebellitis
Alysse Jensen1, Hardik Thakkar1, Scott Kramer1
1Internal Medicine, Moffitt Cancer Center, Tampa, USA.
Immune checkpoint inhibitors (ICIs) are an important treatment modality for advanced cancer. However, they carry the risk of immune-related adverse events (irAEs) secondary to their mechanism of action. ICI medications function by inhibiting the checkpoints that suppress immune cells, which exist to prevent autoimmunity, and prime these cells to attack and eliminate cancer. While ICIs have substantially improved the prognosis for patients with advanced cancer, some patients experience adverse effects from this autoimmune state. One less common, but potentially life-threatening toxicity is cerebellitis. We present a case of anti-glutamic acid decarboxylase 65 (anti-GAD 65) related ICI cerebellitis in a patient with uterine carcinosarcoma on dostarlimab. This patient presented with nonspecific symptoms, including fatigue and a concerning symptom of ataxia. Full neurological evaluation demonstrated anti-GAD 65 antibodies in both her serum and cerebrospinal fluid (CSF). She was unable to start outpatient treatment and was admitted for intravenous steroids and intravenous immunoglobulin (IVIG) with subsequent improvement in her symptoms. She was placed on a prolonged steroid taper with regular IVIG infusions. Her immunotherapy was discontinued. This case report highlights the importance of early clinical suspicion of ICI-related neurotoxicities and rapid treatment initiation. Prompt recognition and early intervention are important to minimize long-term disability.
Immune checkpoint inhibitors (ICIs) are an important treatment modality for advanced cancer. However, they carry the risk of immune-related adverse events (irAEs) secondary to their mechanism of action. ICI medications function by inhibiting the checkpoints that suppress immune cells, which exist to prevent autoimmunity, and prime these cells to attack and eliminate cancer. While ICIs have substantially improved the prognosis for patients with advanced cancer, some patients experience adverse effects from this autoimmune state. One less common, but potentially life-threatening toxicity is cerebellitis. We present a case of anti-glutamic acid decarboxylase 65 (anti-GAD 65) related ICI cerebellitis in a patient with uterine carcinosarcoma on dostarlimab. This patient presented with nonspecific symptoms, including fatigue and a concerning symptom of ataxia. Full neurological evaluation demonstrated anti-GAD 65 antibodies in both her serum and cerebrospinal fluid (CSF). She was unable to start outpatient treatment and was admitted for intravenous steroids and intravenous immunoglobulin (IVIG) with subsequent improvement in her symptoms. She was placed on a prolonged steroid taper with regular IVIG infusions. Her immunotherapy was discontinued. This case report highlights the importance of early clinical suspicion of ICI-related neurotoxicities and rapid treatment initiation. Prompt recognition and early intervention are important to minimize long-term disability.
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