Progressive leucoencephalopathy with macrocephaly, optic atrophy, epileptic seizures, and primary ovarian dysfunction with relative preservation of cognitive functions

• Published in: Neuropediatrics
• Main Authors: Ramantani, G, Hahn, G, Hübner, A, von der Hagen, M, Ikonomidou, H
• Format: Conference Proceeding
• Language: English
• Published: 20.09.2006
• ISSN: 0174-304X; 1439-1899
• DOI: 10.1055/s-2006-953588

Introduction: Disorders of the white matter are a common central nervous system manifestation of inborn errors of metabolism. Case report: We report on a female subject who presented with nystagmus, macrocephaly, oscillating head movements and pes equinus at the age of 9 months. At the age of 10 years, opticus atrophy and epileptic seizures added to the progressing motor dysfunction and increasing spasticity. A primary ovarian dysfunction was diagnosed at the age of 13 years. After an initially normal speech development, she developed progressive dysarthria, while only minor decline of cognitive function was established over the years. Consecutive oral application of L-Dopa and Trihexyphenidyl over several months did not result in any improvement of motor function. At the age of 17 years the patient presents with ataxia, tetraspasticity and refractory focal epilepsy. Results: Cranial magnetic resonance imaging (cMRI) at the age of 17 years shows white matter abnormalities extending into the globus pallidum. Abnormalities of the brain stem involve the superior cerebellar peduncles, the pyramids and the deep cerebellar white matter. Serial cMRIs over a time period of 10 years revealed a drastic increase in the extent of lesions over time, while lactate values remained normal in serum and CSF. There was no evidence of an infectious or autoimmune process during the course of the disease. MR-spectroscopy at the age of 12 years showed a non-specific increase of creatin and inositol. Electroneurography over the course of the disease revealed an axonal and demyelinating neuropathy pronounced at the lower limbs. Molecular genetic analyses and extensive metabolic screening brought no evidence of M. Pelizaeus-Merzbacher, M. Hallervorden-Spatz, “vanishing white matter disease“, ceroid lipofuscinosis, LHON mutation of mtDNA or disorders of amino acid metabolism, sulfatase, peroxisomal or lysosomal enzyme disorders. Endocrine analyses revealed an ovarian dysfunction resulting from primary hypogonadism. Conclusion: We describe the clinical course and serial MRI imaging of a girl with progressive leucoencephalopathy and motor regression associated with macrocephaly, symptomatic epilepsy, and ovarian dysfunction. The patient surprisingly shows preserved cognitive functions despite the progressive leucoencephalopathy most evident in the globus pallidum and brainstem. In spite of extensive laboratory investigations, disease pathology remains unclear.