Porencephaly, an encephaloclastic brain lesion, is one of the most frequent causes of infantile cerebral palsy. This lesion results mainly from ischemic insults occurring in late pregnancy or in early postnatal life or from intrauterine exposure to infections and toxins. The identification of mutations in the COL4A1 and COL4A2 genes, which encode the type IV alpha1 and alpha2 collagen chains, has demonstrated that a subset of porencephaly may be genetically determined. In this article, the author reviews the clinical features and the pathogenetic aspects of porencephaly and provides an update on the pathophysiology of this disorder. Moreover, the author summarizes findings on the role of mutations in COL4A genes in determining small vessel disease and brain malformations. The phenotypic spectrum of mutations of the COL4A genes, which besides cerebrovascular damage may include systemic involvement with ocular, renal, muscular, and cardiac features, is progressively widening. COL4A1/2 gene mutations, originally reported to be associated with familial porencephaly, are in fact increasingly recognized as causative genes of an array of brain malformations, including schizencephaly, polymicrogyria, and subependymal heterotopia, as well as of minor, nonspecific brain abnormalities.
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• Porencephalies are focal cavitary lesions frequently communicating with the lateral ventricles; they result from brain destruction during late fetal or early postnatal developmental stages.
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• The more common etiologic factors are ischemic and hemorrhagic insults, but toxic agents, infections, trauma, and drugs have also been reported.
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• Porencephaly may also be due to dominant mutations (either inherited and de novo) of genes COL4A1 and COL4A2 encoding for type IV collagen alpha-1 and for type IV collagen alpha-2, respectively. The type IV collagen, which is a component of nonfibrillary collagen, is a main constituent of the basement membrane of many tissues, among them vascular endothelia.
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• The clinical expression of the porencephaly depends on its site, its size, and the timing of the causative insult. Clinical symptoms include motor deficits, intellectual impairment, and seizures.
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• The management of porencephaly is that of the associated clinical manifestations: cerebral palsy, intellectual impairment, and seizures. Management includes rehabilitation and antiepileptic treatment. Patients with drug-resistant epilepsy may benefit from respective surgery, which may consist of functional hemispherectomy in patients with large, hemispheric cysts.
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• Genetic counseling is appropriate in familial and genetically determined porencephaly. Special attention in genetic counseling must be paid for families carrying COL4A mutations, given the variable phenotypic expression and penetrance.
Historical note and terminology
The term "porencephaly" (from the Latin word porus, meaning "communication") was first introduced by Heschl in 1859 to describe clefts or cavities in the cerebral mantle (27). He attributed these lesions to destruction of the developing brain. Since Heschl's first description, the term "porencephaly" has been widely used to describe etiologically different brain cavities communicating with either the subarachnoid space or the lateral ventricles.
The present understanding of the term "porencephaly" is still debated. Most authors recognize 2 major subgroups: (1) developmental or true porencephaly, and (2) congenital or encephaloclastic porencephaly. The former refers to cases characterized by full-thickness defects of cortical mantle associated with polymicrogyria or heterotopic gray matter. For these cases, however, the term "schizencephaly" is preferred (22). The second subgroup refers to lesions arising from cortical destruction in the developing brain. Reports of COL4A1 and COL4A2 mutations, both in porencephaly and schizencephaly, suggest that a common genetic mechanism may be responsible for brain damage at least in a subset of patients (69; 09). Nevertheless, from a clinical point of view, schizencephaly and porencephaly must be differentiated because the MRI pictures, the clinical and epileptic phenotypes, and the outcome have distinctive features.