Neurophysiological abnormalities in adrenoleukodystrophy carriers. Evidence of different degrees of central nervous system involvement

Abstract

We studied 19 women, heterozygous for adrenoleukodystrophy (ALD) in whom the carrier status was demonstrated by abnormally high plasma levels of very-long-chain fatty acids. Clinical examination revealed slight neurological signs in two patients. Clear-cut neurological deficits in three, and it was fully normal in the remaining 14. All subjects underwent motor evoked potential (MEP) and somatosensory evoked potential (SEP) studies. Seventeen out of 19 subjects underwent brain MRI which demonstrated various degrees of abnormality in one asymptomatic and five symptomatic subjects; SEPs and MEPs revealed CNS involvement in 12 and 8 out of the 19 subjects, respectively. Symptomatic patients showed severe neurophysiological abnormalities, whereas milder but unequivocal EP abnormalities were found in seven of the 14 patients with normal clinical examination. Our data thus suggest CNS involvement in the majority of the ALD carriers, evident also in preclinical stages and progressively severe. The possibility of assessing different degrees of neurological involvement could be relevant for therapeutical purposes. Moreover, neurophysiological studies could provide the only objective marker of functional nervous system involvement, e.g. in order to monitor the efficacy of treatment, and in clinically and radiologically silent cases.