Widening the MRI Findings of PLA2G6-Associated Neurodegeneration

A 19-year-old male presented with a history of motor and language regression since 5 years of age. Other subsequent symptoms were cognitive decline, ataxia, and kinetic tremor. Brain MRI showed cerebellar hypoplasia and atrophy, clava hypertrophy, and symmetric areas of iron deposition distributed into the substantia nigra, globus pallidi, and fornix ([Fig. 1A–F]). Due to concern for a neurodegeneration with brain iron accumulation (NBIA) disorder, genetic testing was sent that revealed compound heterozygous variants in PLA2G6, c.986G > A (p.Arg329His), a known pathogenic variant, and c.1675C > T (p.Pro559Ser), a variant of unknown significance. Given the clinical history and imaging findings, the c.1675C > T variant was determined to be pathogenic which established a final diagnosis of atypical neuroaxonal dystrophy (NAD) or childhood-onset PLA2G6-associated neurodegeneration (PLAN). Atypical NAD along with infantile NAD (infantile-onset PLAN) and PLA2G6-associated dystonia parkinsonism (adult-onset PLAN) represent the clinical spectrum of disorders caused by PLA2G6 mutations, all of which are characterized by brain iron accumulation.[1] [2] The classic imaging features observed in this case along with some particular findings, including iron deposition in the fornix, and a selective T2-weighted imaging (WI) hyperintensity of the medial medullary lamina in the globus pallidum expands the imaging description of this entity.

Fig. 1 Brain MRI. Sagittal T1-weighted image (T1WI) (A) demonstrates vermian cerebellar atrophy and hypertrophy of the Clava (asterisk). Axial susceptibility-weighted image (SWI) and T1WI (B, C) show a selective involvement of the substantia nigra with iron deposition characterized by low signal intensity on the SWI (B) and hyperintensity on T1WI (C). Axial T2WI, SWI, and T1WI (D–F) show the presence of iron deposition in the globus pallidum characterized by a low signal intensity on T2WI and SWI, and hyperintense signal on T1WI (arrowhead, D–F), sparing the medial medullary lamina (short arrow, D and E), in addition to a selective involvement of the fornix (D–F). MRI, magnetic resonance imaging.

Publikationsverlauf

Eingereicht: 23. März 2021

Angenommen: 19. Mai 2021

Artikel online veröffentlicht:
13. Juli 2021

• References

• 1 Hayflick SJ, Kurian MA, Hogarth P. Neurodegeneration with brain iron accumulation. Handb Clin Neurol 2018; 147: 293-305
• 2 Kurian MA, Morgan NV, MacPherson L. et al. Phenotypic spectrum of neurodegeneration associated with mutations in the PLA2G6 gene (PLAN). Neurology 2008; 70 (18) 1623-1629