Cerebroretinal microangiopathy with calcifications and cysts.
BACKGROUND
Extensive cerebral calcifications and leukoencephalopathy have been reported in two rare disorders Coats plus and leukoencephalopathy with calcifications and cysts. In the latter, a progressive formation of parenchymal brain cysts is a special feature, whereas Coats plus is characterized by intrauterine growth retardation, bilateral retinal telangiectasias and exudations (Coats disease), sparse hair, and dysplastic nails without cyst formation.


METHODS
We identified 13 patients, including two pairs of siblings, with extensive cerebral calcifications and leukoencephalopathy. We reviewed clinical, ophthalmologic, radiologic and neuropathologic data of seven deceased patients and studied five patients prospectively.


RESULTS
Eleven patients were small for gestational age; the other symptoms emerged from infancy to adolescence. All patients had neurologic symptoms including seizures, spasticity, dystonia, ataxia, and cognitive decline. Progressive intracerebral calcifications involved deep gray nuclei, brainstem, cerebral and cerebellar white matter, and dentate nuclei and were accompanied by diffuse white matter signal changes and, in five patients, cerebral cysts. Eleven patients had retinal telangiectasias or angiomas. Additional features were skeletal and hematologic abnormalities, intestinal bleeding, and poor growth. Neuropathologic examination showed extensive calcinosis and abnormal small vessels with thickened, hyalinized wall and reduced lumen.


CONCLUSIONS
Our data suggest that Coats plus syndrome and leukoencephalopathy with calcifications and cysts belong to the same spectrum. The primary abnormality seems to be an obliterative cerebral angiopathy involving small vessels, leading to dystrophic calcifications via slow necrosis and finally to formation of cysts and secondary white matter abnormalities.
Linnankivi
T
T
Department of Pediatric Neurology, Hospital for Children and Adolescents, University of Helsinki, Stenbäckinkatu 11, FIN-00290 Helsinki, Finland. tarja.linnankivi@kolumbus.fi
Valanne
L
L
Paetau
A
A
Alafuzoff
I
I
Hakumäki
J M
JM
Kivelä
T
T
Lönnqvist
T
T
Mäkitie
O
O
Pääkkönen
L
L
Vainionpää
L
L
Vanninen
R
R
Herva
R
R
Pihko
H
H
D000293:Adolescent; D001847:Bone Diseases / Q000000981:diagnostic imaging / Q000209:etiology; D001927:Brain Diseases / Q000175:diagnosis / Q000209:etiology*; D002114:Calcinosis / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000150:complications* / Q000473:pathology; D002675:Child, Preschool; D003560:Cysts / Q000209:etiology*; D005260:Female; D006391:Hemangioma / Q000150:complications; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000175:diagnosis / Q000209:etiology; D008279:Magnetic Resonance Imaging; D008297:Male; D008833:Microcirculation; D012164:Retinal Diseases / Q000150:complications* / Q000175:diagnosis; D019572:Retinal Neoplasms / Q000150:complications; D012171:Retinal Vessels; D013577:Syndrome; D013684:Telangiectasis / Q000150:complications; D014057:Tomography, X-Ray Computed