Brain lactic alkalosis in Aicardi-Goutières syndrome.
Aicardi-Goutières syndrome is a rare progressive encephalopathy characterized by acquired microcephaly, basal ganglia calcification, and chronic CSF lymphocytosis, raised levels of interferon alpha in CSF and plasma and chill-blain type lesions. A possible mechanism of injury is cytokine related microangiopathy. We report brain imaging and proton (1H) and phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) findings during the first year after birth in two patients. In patient 1 the evolution of brain metabolite ratios and intracellular pH obtained from serial 1H (long TE) and 31P MRS studies are described; in patient 2 a single 1H (short TE) MRS study is described. Imaging findings included basal ganglia calcifications, cerebral atrophy, and leukodystrophy. The MRS results demonstrated that Aicardi-Goutières syndrome is associated with reduced NAA/Cr, reflecting decreased neuronal/axonal density or viability, increased myo-inositol/Cr, reflecting gliosis or osmotic stress and a persisting brain lactic alkalosis. A brain lactic alkalosis has also been observed in those infants surviving perinatal hypoxia-ischaemia but with a poor neurodevelopmental outcome. A possible mechanism leading to brain alkalosis is up-regulation of the Na+/H+ transporter by focal areas of ischaemia related to the microangiopathy or by pro-inflammatory cytokines. Such brain alkalosis may be detrimental to cell survival and may increase glycolytic rate in astrocytes leading to an increased production of lactate.
Robertson
N J
NJ
Department of Paediatrics, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK. n.robertson@ucl.ac.uk
Stafler
P
P
Battini
R
R
Cheong
J
J
Tosetti
M
M
Bianchi
M C
MC
Cox
I J
IJ
Cowan
F M
FM
Cioni
G
G
D000471:Alkalosis / Q000378:metabolism*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001479:Basal Ganglia / Q000473:pathology; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001928:Brain Diseases, Metabolic / Q000000981:diagnostic imaging / Q000378:metabolism*; D002114:Calcinosis / Q000473:pathology; D003404:Creatinine / Q000378:metabolism; D004453:Echoencephalography; D006801:Humans; D007231:Infant, Newborn; D019344:Lactic Acid / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013577:Syndrome; D014057:Tomography, X-Ray Computed
D001224:Aspartic Acid; D019344:Lactic Acid; C000179:N-acetylaspartate; D003404:Creatinine