SUN-619 - Riding the Catecholamine Storm: Navigating Type 2 Diabetes Amidst Paroxysmal Sympathetic Hyperactivity due to NMDA Encephalitis

The NMDA receptor modulates CNS excitatory transmission. In anti-NMDAR (NMDAR) encephalitis, autoantibody-mediated dysregulation causes psychiatric symptoms and autonomic instability. A critical complication is Paroxysmal Sympathetic Hyperactivity (PSH), presenting as episodes of tachycardia, hypertension, hyperthermia, diaphoresis, and dystonia. Comorbid T2DM adds complexity, as PSH-induced catecholamine surges and glucocorticoids cause rapid oscillations between hyperglycemia and hypoglycemia. Managing T2DM in this context extends beyond standard protocols and requires an individualized approach to address glycemic volatility.

A 38-year-old male with T2DM on semaglutide presented to trauma with self-inflicted stab wounds to the neck. Following stabilization, he was diagnosed with acute psychosis; however, antipsychotics yielded no improvement. He then developed fevers, tachycardia, and progressive encephalopathy. Initial MRI, LP, and EEG were unrevealing. As cognition declined, he manifested paroxysmal right head deviation and left sided tonic-clonic movements, associated with autonomic surges, only partially responsive to benzodiazepines. Repeat LP confirmed anti-NMDAR encephalitis.

Despite initiation of PLEX, clinical status remained poor. He was transitioned to rituximab and glucocorticoids. He began to have an increasing frequency of his tonic-clonic movements with associated sympathetic hyperactivity- along with worsening dysglycemia. Interdisciplinary review diagnosed PSH. Following treatment with baclofen, propranolol, and gabapentin, his PSH symptoms improved. This led to a precipitous drop in insulin requirements and subsequent hypoglycemic events. When his dysglycemia stabilized, he was discharged on a basal-bolus insulin regimen with outpatient monitoring.

The pathophysiology of NMDAR encephalitis is not well understood, but a proposed mechanism involves the dysregulation of the HPA axis, leading to an ACTH and catecholamine surge. While our patient received glucocorticoids, this did not cause major adjustments in his insulin. However, when he had increasing episodes of PSH, he needed rapid up-titration of his insulin regimen. Following PSH stabilization, insulin requirements plummeted, leading to multiple hypoglycemic events. This suggests PSH-driven surges, rather than glucocorticoids alone, dictated his extreme glycemic volatility.

Patients with NMDAR encephalitis who develop PSH tend to have longer hospitalizations and poorer outcomes. Patients with co-morbid T2DM add an additional layer of complexity, necessitating intensive glycemic monitoring and frequent insulin adjustments. In this patient, the PSH contributed more to his glycemic lability than the glucocorticoids, and early diagnosis and management of PSH is essential to stabilize glycemic control and mitigate further clinical deterioration.

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