Progressive cavitating leukoencephalopathy: A novel childhood disease

Sakkubai Naidu, Genila Bibat, Doris Lin, Peter Burger, Peter Barker, Sergio Rosemberg, Nancy Braverman, Hugo Arroyo, Michael Dowling, Ada Hamosh, Virginia Kimonis, Carol Blank, Agata Fiumara, Sergio Facchini, Bhim Singhal, Hugo Moser, Richard Kelley, Salvatore DiMauro

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


We report 19 patients with a previously undelineated neurodegenerative syndrome characterized by episodic acute onset of irritability or neurological deficits between 2 months and 3.5 years of age, followed by steady or intermittent clinical deterioration. Seven children died between 11 months and 14 years of age. Cranial magnetic resonance imaging (MRI) shows patchy leukoencephalopathy with cavities, and vascular permeability, in actively affected regions. Early lesions affect corpus callosum and centrum semiovale, with or without cerebellar or cord involvement. After repeated episodes, areas of tissue loss coalesce with older lesions to become larger cystic regions in brain or spinal cord. Diffuse spasticity, dementia, vegetative state, or death ensues. Gray matter is spared until late in the course. In some, incomplete clinical or MRI recovery occurs after episodes. The clinical course varies from rapid deterioration to prolonged periods of stability that are unpredictable by clinical or MRI changes. Elevated levels of lactate in brain, blood, and cerebrospinal fluid, abnormal urine organic acids, and changes in muscle respiratory chain enzymes are present but inconsistent, without identifiable mitochondrial DNA mutations or deletions. Pathological studies show severe loss of myelin sparing U-fibers, axonal disruption, and cavitary lesions without inflammation. Familial occurrence and consanguinity suggest autosomal recessive inheritance of this distinct entity.

Original languageEnglish (US)
Pages (from-to)929-938
Number of pages10
JournalAnnals of Neurology
Issue number6
StatePublished - Dec 1 2005

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


Dive into the research topics of 'Progressive cavitating leukoencephalopathy: A novel childhood disease'. Together they form a unique fingerprint.

Cite this