Megalencephalic Leukoencephalopathy With Subcortical Cysts in an Adult

Figure

a) Coronary FLAIR- and b) axial T2-weighted MRI show a symmetric cerebral leukoencephalopathy with confluent hyperintensities of bihemispheric white matter up to the corticomedullary junction (*), bitemporal subcortical cysts of CSF signal (^) and megalencephaly with brain atrophy consistent with megalencephalic leukoencephalopathy with subcortical cysts in an older adult. A cavum septi pellucidi and Vergae (#) constitutes a secondary finding.

A 58-year-old male patient was referred for a brain MRI because of worsening spasticity. His previous diagnosis—after an unremarkable pregnancy and delivery—was infantile cerebral palsy with hydrocephalus and epileptic seizures. Additionally, herpes encephalitis had been suspected. From his 3^rd month of life, a developmental motor delay was noted and megalencephaly developed subsequently. His gait was impaired by spasticity from the outset. The patient graduated from secondary school, completed training and was employed part-time (50%) up to his 50th year of life. In addition to megalencephaly, brain MRI (Figure a and b) showed confluent cerebral leukoencephalopathy and bitemporal cysts. On the basis of the pathognomonic aspect, megalencephalic leukoencephalopathy with subcortical cysts (MLC) was suspected and diagnostic exome sequencing was initiated. Two likely pathogenic compound heterozygous variants (c.274C>T;p.Pro92Ser and c.268–2A>G;p.?) were identified in the MLC1-gene. To our knowledge, this is the oldest patient with this rare disease whose case was published worldwide. It is unclear to which extent the specific genotype (co-) determined the patient’s high level of cognitive functioning and longevity. The diagnosis accounts for his gradually progressive spasticity. Treatment remains symptomatic. An international MLC registry is currently being established in Amsterdam.

PD Dr. med. Andreas Joachim Bartsch, Radiologie Bamberg und Neuroradiologie, Universitätsklinikum Heidelberg; WIN/FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, [e-mail]

Prof. Dr. med. Marjo van der Knaap, Amsterdam Leukodystrophy Center, Amsterdam University Medical Center und VU University Amsterdam

Conflict of interest statement: The authors declare that no conflict of interest exists.

Cite this as: Bartsch AJ, van der Knaap M: Megalencephalic leukoencephalopathy with subcortical cysts in an adult. Dtsch Arztebl Int 2024; 121: 702. DOI: 10.3238/arztebl.m2024.0086