Widespread pH abnormalities in patients with malformations of cortical development and epilepsy: a phosphorus-31 brain MR spectroscopy study.
BACKGROUND
Neuroimaging studies demonstrate that not only the lesions of malformations of cortical development (MCD) but also the normal-appearing parenchyma (NAP) present metabolic impairments, as revealed with (1)H-MRS. We have previously detected biochemical disturbances in MCD lesions with phosphorus-31 magnetic resonance spectroscopy (31P-MRS). Our hypothesis is that pH abnormalities extend beyond the visible lesions.


METHODS
Three-dimensional 31P-MRS at 3.0 T was performed in 37 patients with epilepsy and MCD, and in 31 matched-control subjects. The patients were assigned into three main MCD subgroups: cortical dysplasia (n=10); heterotopia (n=14); schizencephaly/polymicrogyria (n=13). Voxels (12.5 cm3) were selected in five homologous regions containing NAP: right putamen; left putamen; frontoparietal parasagittal cortex; right centrum semiovale; and left centrum semiovale. Robust methods of quantification were applied, and the intracellular pH was calculated with the chemical shifts of inorganic phosphate (Pi) relative to phosphocreatine (PCr).


RESULTS
In comparison to controls and considering a Bonferroni adjusted p-value <0.01, MCD patients presented significant reduction in intracellular pH in the frontoparietal parasagittal cortex (6.985±0.022), right centrum semiovale (7.004±0.029), and left centrum semiovale (6.995±0.030), compared to controls (mean values±standard deviations of 7.087±0.048, 7.096±0.042, 7.088±0.045, respectively). Dunnet and Dunn tests demonstrated that the differences in pH values remained statistically significant in all MCD subgroups. No significant differences were found for the putamina.


CONCLUSIONS
The present study demonstrates widespread acidosis in the NAP, and reinforces the idea that MCD visible lesions are only the tip of the iceberg.
Department of Radiology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. Electronic address: celi.andrade@usp.br.
Celi Santos
CS
Andrade
Department of Radiology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Maria Concepción García
MC
Otaduy
Department of Psychiatry, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Kette Dualibi Ramos
KD
Valente
Department of Radiology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Eun Joo
EJ
Park
Department of Radiology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Alexandre Fligelman
AF
Kanas
Department of Radiology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Mauricio Ricardo Moreira da
MR
Silva Filho
Department of Statistics, Universidade Estadual Paulista Julio de Mesquita Filho, São Paulo, Brazil.
Miriam Harumi
MH
Tsunemi
Department of Radiology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Claudia Costa
CC
Leite
D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D004827:Epilepsy / Q000150:complications* / Q000473:pathology*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D021621:Imaging, Three-Dimensional; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D054220:Malformations of Cortical Development / Q000150:complications* / Q000473:pathology*; D008875:Middle Aged; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus; D055815:Young Adult
D010725:Phosphocreatine; D010758:Phosphorus
Epilepsy; Magnetic resonance imaging; Malformations of cortical development; Neurometabolism; Phosphorus spectroscopy