[Physiopathology of periventricular leukomalacia]

The term "periventricular leukomalacia" (PVL) usually covers necrotic and/or gliotic lesions from perinatal origin occurring in the periventricular ring of telencephalic white matter. However focal white matter necrosis is often associated to a diffuse white matter disease and to brainstem and grey matter lesions, making up the basis of a true encephalopathy. PVLs are diagnosed in 4% to 10% of infants born before 33 weeks of gestation. The proportion of PVLs from prenatal origin is estimated around one third of cases. Recent progresses in neuroepidemiology, developmental neurobiology and imaging methods permitted to revisit the pathophysiology of PVLs on a multifactorial basis. The end result of these multiple factors seems to be calcium influx due to glutamatergic overactivation triggered by cytokines, free radicals, and deficits in neurotrophic factors. Periventricular topography can be explained by properties of the brain at this specific step of brain development. Carrying motor and neuropsychological consequences, PVLs could be the most severe danger for very premature brains. Positive rolandic sharp waves recorded on EEG and precocious abnormally echogenous periventricular images on ultrasound suggest prospective periventricular cysts. Cystic periventricular cavitations certify the diagnosis of PVL. More subtle lesions of PVL do not reach the cystic grade and their diagnosis is confirmed by MRI. Treatment of infections is already available and potentially a tool for prevention. When the overwhelming glutamatergic signal has been triggered, neuroprotective agents turning off the excitotoxic cascade, including calcium blockers, growth factors and others, are promising therapeutic tools.