Polymicrogyria is a complex malformation of cortical development due to disorder of neuronal organization, in which the process of normal cerebral cortical development is disturbed in an early stage of cortical organization. Macroscopically or grossly, including by MRI, it is defined by clusters of gyri that are too small and too numerous for the area. Microscopically, not only are there numerous gyri in clusters but also many of the gyri are fused to adjacent gyri with continuity of their molecular zones and synaptic activity without the normal intervening subarachnoid space with leptomeninges and small meningeal blood vessels. Lamination of the cortex of these gyri also is abnormal with many displaced and disoriented neurons of all types, but there are no dysplastic megalocytic neurons as seen in focal cortical dysplasia type II, hemimegalencephaly, or tuberous sclerosis, except in some cases associated with a somatic mutation in the mTOR signaling pathway. Discontinuities or gaps in the pial membrane and lamina limitans, including the fetal subpial granular glial layer of Brun, are morphological features that lead to gyral fusion. Synaptic continuity of fused molecular zones (of mostly excitatory synapses) of adjacent microgyria results in epileptogenic short-circuitry. Clinical manifestations of perisylvian polymicrogyria include epilepsy, speech and language disturbance, and cognitive deficits, but polymicrogyria can be associated with many genetic syndromes with additional neurologic impairments; the spectrum of genes identified in polymicrogyria is very large, hence it is a heterogenous malformation.
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• Polymicrogyria is a cerebral malformation of cortical development with excessive folding of small, numerous fused gyri and normal or abnormal cortical lamination.
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• Fusion of gyri microscopically results in continuity of the molecular zone of adjacent small gyri without intervening pial membranes or leptomeninges; pathogenesis involves discontinuities in the pia of the cortex during gyration or sulcation after mid-gestation.
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• The underlying etiologies are multiple but can be summarized into 3 categories: (1) genetic disorders; (2) association with other malformations of the brain, such as schizencephaly and cerebellar dysplasia; and (3) vascular infarcts or ischemic zones, resulting in a wide variety of neurologic signs and symptoms.
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• The distribution of polymicrogyria most frequently is perisylvian; it always is associated with schizencephaly, but in other cases it may be focal in any lobe or can be generalized throughout the cortex of both hemispheres.
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• High-resolution MRI is the most reliable imaging modality for diagnosis and evaluating the distribution and extent of the dysgenesis and association with other brain malformations; fMRI shows decreased activation; neuropathology provides microscopic details not revealed by imaging.
• The most constant clinical manifestations include epilepsy and sometimes even severe infantile epilepsies, cognitive impairment, and speech and language disturbance in perisylvian polymicrogyria. Many other findings in both brain and body occur with polymicrogyria in the various genetic syndromes.
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• Surgical resection of epileptogenic foci within polymicrogyria may provide good seizure control with better developmental outcome in children, but polymicrogyria is not always epileptogenic.
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• Neuroanatomical features at the single neuron level determine epileptic potential by shifting the excitatory/inhibitory ratio: short circuitry of the molecular zones of adjacent fused gyri, paucity of keratan sulfate inhibition of glutamatergic synapses, and clustering of Cajal-Retzius neurons that cause dyslamination of the cortical plate in microgyria.
Historical note and terminology
Originally coined in the early 1900s by Bielschowsky (96), the term, “polymicrogyria” was largely replaced by the term “microgyria” by the middle of the 20th century. Contemporary preference has seen a resurgence of the term “polymicrogyria,” which more accurately describes the findings in this disorder (97).
Classification. Several types with various manifestations and etiologies have been noted. Under the current classification of malformations of cortical development, the following types of polymicrogyria are defined by MRI (09; 08). They also can be so classified by gross neuropathology.
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(1) Bilateral frontal polymicrogyria (BFP)
(2) Bilateral frontoparietal polymicrogyria (BFPP)
(3) Bilateral perisylvian polymicrogyria (BPP)
(4) Bilateral parasagittal parieto-occipital polymicrogyria (BPPOP)
(5) Bilateral generalized polymicrogyria (BGP)
(6) Unilateral perisylvian polymicrogyria (UPP) (09)
Outdated names used for polymicrogyria include microgyria, micropolygyria, and status verrucosus deformis (33).