Acute Necrotizing Encephalopathy and Cerebral Infarction Triggered by Mycoplasma pneumoniae Infection in a Pediatric Patient: A Rare Clinical Association

To the Editors: Mycoplasma pneumoniae (M. pneumoniae) is a major pathogen of community-acquired pneumonia in children, with neurologic complications occurring in approximately 2.6%–9.1% of cases.1 Acute necrotizing encephalopathy (ANE), a rare but severe neurological complication, is typically associated with viral infections, and only 6 cases linked to M. pneumoniae have been reported to date.2–6 Here, we present a unique case of a 6-year-old boy with M. pneumoniae infection complicated by ANE and vertebrobasilar artery occlusion, highlighting its distinct clinical features and pathogenic implications. The patient initially presented with fever and cough, progressing to headache, vomiting, left limb weakness and convulsions 5 days later. On admission, he required intubation with a Glasgow Coma Scale score of 3T (E1VTM2), and exhibited absent brainstem reflexes and bilateral Babinski signs. Laboratory findings showed elevated procalcitonin (7.4 ng/mL), C-reactive protein (56.8 mg/L) and interleukin-6 (107 pg/mL), along with coagulation abnormalities (prolonged prothrombin time, elevated D-dimer, reduced fibrinogen). M. pneumoniae RNA with macrolide resistance mutations was detected in throat swab. Cerebrospinal fluid analysis showed markedly elevated protein (1258 mg/L), IL-6 (1630.3 pg/mL) and IL-8 (9774.2 pg/mL), with negative pathogens. Whole-exome sequencing excluded known pathogenic variants. Initial chest computed tomography revealed bilateral pulmonary consolidations with cavitation. Subsequent brain magnetic resonance imaging on day 2 showed diffuse hyperintensities in the medulla oblongata, bilateral cerebellar and cerebral hemispheres, consistent with encephalitis. By day 6, magnetic resonance imaging demonstrated symmetric hyperintense lesions in the bilateral thalami, pons and cerebellum, with diffuse cerebral edema, restricted diffusion and hemorrhagic necrosis, strongly suggestive of ANE. Computed tomography angiography and magnetic resonance angiography confirmed segmental occlusions in the right vertebral artery, basilar artery and posterior cerebral artery, indicative of cerebral infarction. Serial imaging findings were summarized in Figure 1.FIGURE 1.: A (CT): Low-density lesions in bilateral thalamus; cerebral infarction with hemorrhagic reperfusion in the right occipitoparietal lobe and paraventricular region. B and C (T2WI/DWI): Symmetric thalamic hyperintensities (T2WI) with mixed signals (DWI). D (MRA): Nonvisualization of right vertebral artery and basilar artery; severe stenosis of right posterior cerebral artery. CT indicates computed tomography; DWI, diffusion-weighted imaging; MRA, magnetic resonance angiography; T2WI, T2-weighted imaging.Treatment included levofloxacin, anticoagulation, intracranial pressure control and mechanical ventilation. Immunomodulation included intravenous immunoglobulin (2 g/kg over 3 days), high-dose methylprednisolone (20 mg/kg/day for 3 consecutive days), tocilizumab and plasma exchange. Despite resolving the pulmonary infection, the neurological status remained poor. The patient was discharged with cerebral failure and died one week later. While ANE typically presents with symmetric thalamic lesions secondary to viral-induced cytokine storms, M. pneumoniae-associated ANE is exceedingly rare. Our case is distinguished by the coexistence of ANE and vertebrobasilar infarction, likely driven by synergistic mechanisms: immune-mediated vasculitis (supported by elevated cerebrospinal fluid cytokines) and hypercoagulability (evidenced by elevated D-dimer and hypofibrinogenemia), which together may have exacerbated vascular occlusion and blood-brain barrier disruption. Notably, the 5-day interval between respiratory symptoms and neurological deterioration differs from the rapid progression of viral ANE, suggesting a delayed immune-mediated pathogenesis in M. pneumoniae infections.7 This case underscores the need for vigilant monitoring of thrombotic events and central nervous system inflammation in severe M. pneumoniae infections. Further studies are warranted to elucidate the interplay between immune dysregulation and coagulation in such presentations.