PLA2G6-associated neurodegeneration: Lessons from neurophysiological findings

Abstract

Background and aims: Phospholipase A2 associated neurodegeneration (PLAN) is a heterogeneous autosomal recessive disorder caused by mutations in the ubiquitously expressed PLA2G6 gene. It is responsible for delayed brain iron accumulation and induces progressive psychomotor regression. We report the concomitant clinical, radiological and neurophysiological findings in PLAN patients in an attempt to determine the contribution of each test to guide diagnosis.

Methods: Concomitant clinical, radiological, electroencephalographic (EEG) and electrodiagnostic testing (EDX) findings in a series of 8 consecutive genetically confirmed PLAN patients were collected.

Results: All patients presented marked motor axonal loss, with decreased or absent distal compound muscle action potentials, acute and chronic denervation at needle electromyography, in contrast with preservation of sensory conduction. EEG showed high-amplitude fast activity in all patients aged above 15 months. Two patients showing severe neonatal hypotonia displayed atypical hypsarhythmia and epileptic spasms. Iron deposition in globus pallidus was observed in only two patients aged above 6 years.

Conclusions: Peripheral involvement is an early feature in PLAN recognizable by EDX at an earlier stage than typical iron accumulation in the brain. Furthermore, the association of West syndrome and axonal motor neuropathy may represent positive clues in favor of PLAN. This results emphasize the interest of early and repeated EDX.

Keywords: Epileptic spasms; Hypsarhythmia; Infantile neuroaxonal dystrophy; Neuropathy; PLA2G6 gene.