Reverse Shapiro Syndrome Presenting as Fever of Unknown Origin: A Case Report and Review of the Literature

Reverse Shapiro syndrome (RSS) is an exceptionally rare neurological disorder characterized by recurrent episodes of hyperthermia in the context of agenesis of the corpus callosum (ACC), in contrast to the hypothermic episodes seen in classic Shapiro syndrome (SS). The exact pathophysiology remains unclear; however, hypothalamic dysregulation, neurotransmitter imbalances, and melatonergic involvement are believed to play key roles. Herein, we present a case of RSS in a 33-year-old male patient with a medical history of partial agenesis of the corpus callosum and spastic tetraparesis with persistent episodes of unexplained high fever leading to multiple hospitalizations. Endocrine and infectious causes were excluded. Both antibiotics and supportive management failed to resolve the symptoms, whereas levodopa administration led to complete remission of symptoms. Fewer than 10 cases have been reported in the literature to date. Management in reported cases was largely supportive, with mixed responses to pharmacological agents, such as dopamine agonists and serotonin antagonists. Given the potential for diagnostic delay and its impact on patients' quality of life, awareness of RSS is essential in cases of fever of unknown origin, particularly in patients with known or suspected congenital brain anomalies.