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 journalArticle

24 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)929-938
Number of pages10
JournalAnnals of Neurology
Volume58
Issue number6
DOIs
StatePublished - Dec 2005

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Leukoencephalopathies
Magnetic Resonance Imaging
Persistent Vegetative State
Consanguinity
Corpus Callosum
Sequence Deletion
Brain
Capillary Permeability
Myelin Sheath
Electron Transport
Mitochondrial DNA
Cerebrospinal Fluid
Dementia
Lactic Acid
Spinal Cord
Urine
Inflammation
Muscles
Acids
Enzymes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Naidu, S., Bibat, G., Lin, D., Burger, P., Barker, P., Rosemberg, S., ... DiMauro, S. (2005). Progressive cavitating leukoencephalopathy: A novel childhood disease. Annals of Neurology, 58(6), 929-938. https://doi.org/10.1002/ana.20671

Progressive cavitating leukoencephalopathy : A novel childhood disease. / Naidu, Sakkubai; Bibat, Genila; Lin, Doris; Burger, Peter; Barker, Peter; Rosemberg, Sergio; Braverman, Nancy; Arroyo, Hugo; Dowling, Michael; Hamosh, Ada; Kimonis, Virginia; Blank, Carol; Fiumara, Agata; Facchini, Sergio; Singhal, Bhim; Moser, Hugo; Kelley, Richard; DiMauro, Salvatore.

In: Annals of Neurology, Vol. 58, No. 6, 12.2005, p. 929-938.

Research output: Contribution to journalArticle

Naidu, S, Bibat, G, Lin, D, Burger, P, Barker, P, Rosemberg, S, Braverman, N, Arroyo, H, Dowling, M, Hamosh, A, Kimonis, V, Blank, C, Fiumara, A, Facchini, S, Singhal, B, Moser, H, Kelley, R & DiMauro, S 2005, 'Progressive cavitating leukoencephalopathy: A novel childhood disease', Annals of Neurology, vol. 58, no. 6, pp. 929-938. https://doi.org/10.1002/ana.20671
Naidu S, Bibat G, Lin D, Burger P, Barker P, Rosemberg S et al. Progressive cavitating leukoencephalopathy: A novel childhood disease. Annals of Neurology. 2005 Dec;58(6):929-938. https://doi.org/10.1002/ana.20671
Naidu, Sakkubai ; Bibat, Genila ; Lin, Doris ; Burger, Peter ; Barker, Peter ; Rosemberg, Sergio ; Braverman, Nancy ; Arroyo, Hugo ; Dowling, Michael ; Hamosh, Ada ; Kimonis, Virginia ; Blank, Carol ; Fiumara, Agata ; Facchini, Sergio ; Singhal, Bhim ; Moser, Hugo ; Kelley, Richard ; DiMauro, Salvatore. / Progressive cavitating leukoencephalopathy : A novel childhood disease. In: Annals of Neurology. 2005 ; Vol. 58, No. 6. pp. 929-938.
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