title: Progressive cavitating leukoencephalopathy: a novel childhood disease.
abstract: 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.
authors.affiliation: Neurogenetics Department, Kennedy Krieger Institute and the Johns Hopkins Medical Institutions, 707 N. Broadway, 5th Floor Tower, Baltimore, MD 21205, USA. naidu@kennedykrieger.org
authors.forename: SakkuBai
authors.initials: S
authors.lastname: Naidu
authors.forename: Genila
authors.initials: G
authors.lastname: Bibat
authors.forename: Doris
authors.initials: D
authors.lastname: Lin
authors.forename: Peter
authors.initials: P
authors.lastname: Burger
authors.forename: Peter
authors.initials: P
authors.lastname: Barker
authors.forename: Sergio
authors.initials: S
authors.lastname: Rosemberg
authors.forename: Nancy
authors.initials: N
authors.lastname: Braverman
authors.forename: Hugo
authors.initials: H
authors.lastname: Arroyo
authors.forename: Michael
authors.initials: M
authors.lastname: Dowling
authors.forename: Ada
authors.initials: A
authors.lastname: Hamosh
authors.forename: Virginia
authors.initials: V
authors.lastname: Kimonis
authors.forename: Carol
authors.initials: C
authors.lastname: Blank
authors.forename: Agata
authors.initials: A
authors.lastname: Fiumara
authors.forename: Sergio
authors.initials: S
authors.lastname: Facchini
authors.forename: Bhim
authors.initials: B
authors.lastname: Singhal
authors.forename: Hugo
authors.initials: H
authors.lastname: Moser
authors.forename: Richard
authors.initials: R
authors.lastname: Kelley
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D000293:Adolescent; D001706:Biopsy; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005808:Genes, Recessive; D020271:Heredodegenerative Disorders, Nervous System / Q000145:classification* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male