Lateral Geniculate Body Involvement and Optic Atrophy in Acute Necrotizing Encephalopathy

A healthy 6-year-old female, vaccinated apart from the seasonal influenza vaccine, presented with 5 days of fever and cough, followed abruptly by worsening mental status and two generalized tonic-clonic seizures. Nasopharyngeal swab was positive for influenza A antigen, amid a severe influenza season.[1] Serum lactate, liver enzymes, platelets, and inflammatory markers were normal. Cerebrospinal fluid revealed 18 WBC/uL, 418 RBC/uL, glucose 70 mg/dL, and protein 144 mg/dL; multiplex meningoencephalitis PCR was negative. MRI showed multiple foci of restricted diffusion and T2 FLAIR hyperintensity in the bilateral thalami, insula, hippocampi, mamillary bodies, brainstem, and cerebellum ([Fig. 1A]). Whole genome sequencing yielded an autosomal dominant, heterozygous RANBP2 pathogenic variant, c.1754 C > T p.(T585M), predisposing to influenza-associated acute necrotizing encephalopathy (ANE).[2] She received oseltamivir, pulse-dose corticosteroids, and supportive care. Her 90-day modified Rankin score was 3 (moderate disability), marked in part by decreased visual acuity (right 20/40, left count fingers at 3 ft), large-angle left sensory exotropia, and bilateral optic pallor ([Fig. 1B]). Optic atrophy was thought secondary to ANE-related intracranial pressure elevation (unmeasured in this case) and/or lateral geniculate nucleus (LGN) injury causing retrograde trans-synaptic optic nerve Wallerian degeneration.[3] Owing to ANE's potential for intracranial hypertension[4] and LGN involvement,[5] [6] survivors should be screened for neuro-ophthalmic complications.

Fig. 1 (A) Neuroimaging demonstrated diffusely abnormal T2 FLAIR signal most prominently in the bilateral thalami, insula, hippocampi, mamillary bodies, and brainstem. Arrows highlight thalamic hyperintensities in the bilateral LGN of the optic apparatus on corresponding axial and coronal slices, which may underlie chronic, retrograde trans-synaptic optic atrophy and diminished visual acuity in this patient. (B) Ocular fundus photos illustrate bilateral 2+ optic nerve pallor.

Publikationsverlauf

Eingereicht: 05. Mai 2025

Angenommen: 07. Juli 2025

Accepted Manuscript online:
08. Juli 2025

Artikel online veröffentlicht:
14. Juli 2025

• References

• 1 Fazal A, Reinhart K, Huang S. et al. Reports of encephalopathy among children with influenza-associated mortality - United States, 2010-11 through 2024-25 influenza seasons. MMWR Morb Mortal Wkly Rep 2025; 74 (06) 91-95
• 2 Sakuma H, Thomas T, Debinski C. et al. International consensus definitions for infection-triggered encephalopathy syndromes. Dev Med Child Neurol 2025; 67 (02) 195-207
• 3 Jindahra P, Petrie A, Plant GT. Retrograde trans-synaptic retinal ganglion cell loss identified by optical coherence tomography. Brain 2009; 132 (Pt 3): 628-634
• 4 Nosaka N, Tsukahara K, Knaup E. et al. Intracranial pressure monitoring for pediatric acute encephalopathy. Acta Med Okayama 2017; 71 (02) 179-180
• 5 Horváthy-Szőcs A, Liptai Z, Dobner S, Rudas G, Barsi P. A closer investigation of the synchronous bilateral pattern of MRI lesions in acute necrotizing encephalopathy type 1. AJNR Am J Neuroradiol 2021; 42 (12) 2251-2253
• 6 Sarigecili E, Ucar HK, Havali C, Cansu A, Aydin K. Acute necrotizing encephalopathy associated with RANBP2 mutation: value of MRI findings for diagnosis and intervention. Acta Neurol Belg 2023; 123 (02) 571-582