Atlantoaxial instability associated with ALDH18A1 mutation.

We report a 10-year-old boy with a de novo pathogenic variant in ALDH18A1, a rare form of metabolic cutis laxa, which was complicated by atlantoaxial instability and spinal cord compression following a fall from standing height. The patient required emergent cervical spine fusion and decompression followed by a 2-month hospitalization and rehabilitation. In addition to the core clinical features of joint and skin laxity, hypotonia, and developmental delays, we expand the connective tissue phenotype by adding a new potential feature of cervical spine instability. Patients with pathogenic variants in ALDH18A1 may warrant cervical spine screening to minimize possible morbidity. Neurosurgeons, geneticists, primary care providers, and families should be aware of the increased risk of severe cervical injury from minor trauma.

Dexmedetomidine-Associated Hyperpyrexia in Three Critically Ill Patients With Coronavirus Disease 2019.

OBJECTIVES: To present three patients with severe coronavirus disease 2019 infection who developed life-threatening hyperpyrexia while being treated with dexmedetomidine for sedation. DATA SOURCES: Clinical records. STUDY SELECTION: Case report. DATA EXTRACTION: Relevant clinical information. DATA SYNTHESIS: We describe three patients, a 60-year-old female, 43-year-old female, and 46-year-old male, who were hospitalized in surge ICUs during the coronavirus disease 2019 pandemic in the early spring of 2020. All developed hyperpyrexia, defined as a temperature above 41.1°C, following an increase in dexmedetomidine dosing to above 1.5 µg/kg/hr. Fevers resolved following discontinuation of dexmedetomidine. CONCLUSIONS: While the exact mechanism of hyperpyrexia remains unclear, findings in this study suggest that high doses of dexmedetomidine infusion are associated with hyperpyrexia in a seemingly dose-dependent fashion in critically ill patients with coronavirus disease 2019. Coronavirus disease 2019 infection causes a hyperinflammatory state characterized by pro-inflammatory cytokine dysregulation. Dexmedetomidine, a centrally acting alpha-2 agonist, may alter hypothalamic temperature regulation through disturbances in neurotransmitter expression and metabolism. We postulate that the use of high-dose dexmedetomidine in a hyperinflammatory state may increase the risk of developing hyperpyrexia in this severe disease state.