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Deficits Linger in Pediatric Self-Limiting Leukodystrophies


 

PITTSBURGH — Two previously undescribed self-limiting leukodystrophies appear to affect infants and children, leaving them with residual neurologic deficits despite resolution of severe abnormalities of white matter with cavitations, Dr. SakkuBai Naidu, said at the annual meeting of the Child Neurology Society.

Dr. Naidu, director of the neurogenetics unit at the Kennedy Krieger Institute, Baltimore, described the disorders in eight children.

The first unnamed disorder she described occurred in six neonates, two of whom were monozygotic twins. All six infants developed neurologic symptoms within the first week of life. Apathy appeared initially, followed by lethargy and seizures requiring intubation. “The initial magnetic resonance imaging was not informative, except for abnormal diffusion-weighted imaging,” she said in an interview. “However, 2 weeks later, the white matter developed large cystic cavitations throughout the corona radiata.”

At that point, the infants had improved clinically, were weaned from ventilators, and placed on anticonvulsants. They later developed hypotonia progressing to mild spasticity, without recurrence of seizures.

Follow-up MRIs at 1 year showed complete resolution of the cavitations without significant brain atrophy. However, all the infants had cortical blindness and were developmentally delayed.

The second recently discovered leukodystrophy disorder was found in two older children who were healthy and developmentally normal until the second decade of life, Dr. Naidu reported. Initial symptoms were insidious, starting with progressive dementia, and then followed by dystonia, rigidity, and ataxia. Imaging showed a similar kind of bilateral cystic cavitation in the cerebellum with abnormal white matter.

By the end of the second decade of life, however, disease progression had stabilized. Imaging showed that the lesions had improved, although both children were left with residual rigidity, ataxia requiring aids for walking, and dementia.

“The most devastating MRI changes and clinical manifestations in the two conditions appear to have an age-associated onset, but self-limiting course, suggesting that timing identifies specific MRI changes, and time determines the clinical outcome in some disorders,” Dr. Naidu said.

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