The histopathology of polymicrogyria: a series of 71 brain autopsy studies

Abstract

PMG PolymicrogyriaAIM Polymicrogyria (PMG) is one of the most common forms of cortical malformation yet the mechanism of its development remains unknown. This study describes the histopathological aspects of PMG in a large series including a significant proportion of fetal cases.METHOD We have reviewed the neuropathology and medical records of 44 fetuses and 27 children and adults in whom the cortical architecture was focally or diffusely replaced by one or more festooning bands of neurons. RESULTSThe pial surface of the brain overlying the polymicrogyric cortex was abnormal in almost 90% of cases irrespective of the aetiology. This accords with animal studies indicating the importance of the leptomeninges in cortical development. The aetiology of PMG was highly heterogeneous and there was no correlation between cortical layering patterns and aetiology. PMG was almost always associated with other brain malformations. INTERPRETATIONThe inclusion of many fetal cases has allowed us to examine the early developmental stages of PMG. The study indicates the significance of surface signals responsible for human corticogenesis and the complex interaction between genetic and environmental factors leading to this common endpoint of cortical maldevelopment.Polymicrogyria (PMG) is a common and highly heterogeneous malformation of cortical development with variable clinical phenotype, imaging, and histology. 1-3 PMG may cause a variety of symptoms including seizures, developmental delay, motor problems, isolated language delay, feeding problems, microcephaly, and multiple congenital anomalies, all to a variable degree of severity. It usually occurs in association with other brain malformations and/or multiple congenital anomalies or intellectual disability. 1 During life, diagnosis of PMG is based on neuroimaging. The magnetic resonance imaging (MRI) features of PMG consist of an irregular and bumpy appearance of the cortex, with apparent cortical thickening, and a stippled grey-white matter junction.2,4 PMG can be focal or diffuse, unilateral or bilateral. Different imaging patterns have been described including bilateral frontal, frontoparietal, perisylvian, lateral parietal, parasagittal parietooccipital, and generalized, as well as unilateral PMG. 2,[5][6][7][8][9][10][11] Although histology is regarded as the diagnostic criterion standard, post-mortem pathology is rarely obtained. The descriptions in the neuropathological literature are based on patients who died or required surgery for intractable epilepsy and likely represent the most severe end of the spectrum. Detailed examination of fetal brains reveal the cortical malformation in the early developmental stages.The architectonic features of PMG were first described by Bielschowsky in 1915 12 and since by others. [13][14][15][16][17][18] Diagnostic criteria for PMG as defined by Friede in 1989 include abnormal arrangement of cell layers, an intracortical fibre plexus, extensive folding of all layers or of the upper layers only, and fusion of gyral surfaces. 16 Norma...

Aberrant fissure in polymicrogyria

“…We found other brain anomalies in association with PMG in 50% of our patients. This ratio is lower compared to a recent study by Jansen et al in which they stated that PMG is almost always associated with other brain malformations 15 . This may be attributable to the smaller cohort in our study and the difference in that the abovementioned study was a histopathologic one and our MRI study might not have been able to detect all malformations.…”

“…Histologically, there are multiple abnormal small gyri, shallow sulci and fusion of the first molecular layer in PMG 12,13 . Pial defects and abnormal vascular structures were also reported in PMG 14,15 . In addition, cortical infoldings formed by the malformed cortex were also described, however, the MRI properties of these cortical infoldings and undulations have not yet been studied 12 .…”

Malformations of cortical development

“…71 It is probably caused by prenatal damage to the glial limiting membrane. 72 Presentation varies with the location and the extent of the PMG, but most patients have developmental delay or behavioral problems in childhood and 70% develop seizures during the first 5 years of life. 71 Despite the large number of patients affected, PMG pathogenesis is poorly understood: It is very likely multifactorial; its presentation and outcome vary because of its causal heterogeneity; and not all disorders with multiple small gyri are true polymicrogyria, even though they have multiple small gyri and may therefore be given that diagnosis.…”

Participation: remembering the ‘handicap’

“…Handicap referred to the impact that impairment and disability had on the person's role in society or the disadvantage experienced while trying to fulfill certain social roles. 4 From the beginning, the ICIDH system was ill-defined and lacked depth. 5 However, the emerging field of childhood disability adopted its language and principles.…”

“…Mutations of these various genes may lead to radial glial instability via different means, loss of interaction with the basal membrane in the case of GPR56, and cytoskeletal destabilization for TUBB2B. 3 Jansen et al 4 studied the histopathological aspects of PMG in 44 fetuses and 27 children and adults in whom the cortical architecture was focally or diffusely replaced by one or more festooning bands of neurons. They showed that the pial surface of the brain overlying the polymicrogyric cortex was abnormal in almost 90% of their cases irrespective of the aetiology, suggesting an important role for the leptomeninges in cortical development.…”