Schizencephaly …

Harvey B Sarnat MD FRCPC MS

Developmental Malformations

Updated 10.26.2023
Released 07.28.1994
Expires For CME 10.26.2026

Schizencephaly

Author: Harvey B Sarnat MD FRCPC MS

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Schizencephaly

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Introduction

Overview

Schizencephalies are fetal brain disruptions characterized by cerebral clefts lined by dysplastic polymicrogyric cortex extending medially from the pial surface to the lateral ventricles. Schizencephaly is the result of a disruption of cerebral development, most probably arising during the early second trimester of pregnancy. The severity of the clinical picture, made up by motor deficits, intellectual disability, and epilepsy, is related to type, location, and size of the clefts and the presence of associated brain abnormalities and identified genetic defects. Schizencephaly may be unilateral or bilateral and is not limited by gender or ethnicity.

Key points

	• Polymicrogyria, ie, patches of minute gyri are present in open and closed lip schizencephaly, borders the defect. These mini-gyri have pial discontinuities that enable synaptic short-circuiting between adjacent gyri and increase the risk of epilepsy.
	• Schizencephaly associated with porencephaly is secondary to genetic or environmental causes that interfere with circulation resulting in infarction, usually in the middle cerebral arterial territory, but also from venous obstructions.
	• Careful history taking may reveal acquired epigenetic damage in utero (eg, by use of cocaine and other teratogens).
	• Molecular genetic studies may reveal defects commonly associated with hemorrhagic or thrombotic disease, mimicking acquired lesions. The most frequent is COL4A1 mutation.
	• Clinical manifestations include motor deficits (eg, spastic hemiparesis or diparesis), language and intellectual deficits, and epilepsy.
	• Onset of epilepsy is usually in infancy or early childhood but may be delayed even to adult life.

Historical note and terminology

Schizencephalies are congenital clefts that unilaterally or bilaterally extend from the pial surface of the lateral parts of the cerebral cortex to the lateral ventricle. The opposing borders of each separate cleft are covered by abnormal neocortex, structured as polymicrogyria, a developmental anomaly. The presence of polymicrogyria is consistent with an origin during the migratory or early postmigratory period of neocortical development, including lamination of the cortical plate to produce mature cortical organization.

Schizencephaly was first described by Wilmarth in 1887 (102). The term is derived from the Greek word “schizen,” which means to divide and was introduced by Yakovlev and Wadsworth in 1946. There are two types of schizencephaly as defined by these authors: the closed lips and the open lips types (107; 108). In the closed lips type, the defects that connect the arachnoid and ventricular spaces are lined by pial-ependymal seams. The seams merge tightly like a zipper, isolating the arachnoid space from the lateral ventricle. The dysplastic neocortex beneath the seam manifests polymicrogyria, an anomaly of cortical development that is detectable on MRI, adding evidence of the fetal origin of the lesion. The open lips type of schizencephaly presents as an open connection between arachnoid and ventricular spaces. Viewed from the outside of the brain, the opercula are malformed and not fully approximated (87). Some authors attempt to classify schizencephalies by criteria of morphology and other associated brain anomalies such as the state of the septum pellucidum (40).

Porencephaly, an inborn unilateral or bilateral cerebral mantle defect shares some properties with schizencephaly but differs from the latter by the absence of ectopic abnormal grey matter lining the defect. It arises as a later disruption of cerebral development after cortical development has reached a mature stage, with migration of cortical neurons completed. Insights in the morphogenesis of both disorders has deepened in the last decades due to refined imaging techniques and discoveries in the field of genetics. Breedveld and colleagues showed mutations of COL4A1, associated with porencephaly (14). COL4A1 encodes a vascular basement protein, known from previous studies to be involved in cases of cerebral hemorrhage and thrombosis. Yoneda and colleagues showed pathogenic mutations of COL4A1 to be linked to schizencephaly (109). The convergent findings support a link between cases of porencephaly and schizencephaly. From these and later studies it transpires that the morphological difference between schizencephaly and porencephaly depends on the stage of neocortical development at the time of the insult: schizencephaly resulting from a lesion during corticogenesis, whereas porencephaly has its time of origin after a stable ordering of cortical layers is reached. These and other studies point to a vascular/ischemic mechanism underlying schizencephaly. Not all cases are related to genetic defects. Exogenous causes cannot be dismissed. Indeed, epidemiologic findings indicate that exogenous causes interfering with pregnancy have to be considered in addition to genetic defects. Exogenous causes also include cytomegalovirus and possibly toxic agents in early pregnancy including the use of cocaine (49).

Schizencephalies originate in the middle fetal period when neocortical neurons have not yet established their definite place in vertical and horizontal organization and movement of the neuronal somata is still possible. Disruptions affecting the evolution of the neocortex during this period may result in disordered vertical and horizontal register of the cortical layers, presenting as polymicrogyria. Polymicrogyria arises during the neuronal migration period, extending to the stabilization period during which connectivity within and to the outside connections of the neocortex is achieved. Polymicrogyria presents on MRI as very small fused gyri.

Porencephalies are generally thought to arise from a destructive process. Porencephaly and schizencephaly share morphological features, but the term schizencephaly, first coined by Yakovlev and Wadsworth, is reserved for cases in which polymicrogyric cortical tissue overlies the defects (107; 108). These authors emphasized the malformative nature and early ontogenetic origin of schizencephalies. They also distinguished type 1 (or closed-lip) schizencephaly, in which the walls of the cleft are in contact with each other, and type 2 (or open-lip) schizencephaly, characterized by separated lips and cerebrospinal fluid-filled clefts. Although type 1 is well defined, type 2 is much more diverse in shape, extent, and associated abnormal findings. In some patients bilateral schizencephaly may be closed on one side and open on the other side.

Coronal section of cerebrum of adult with schizencephaly

On the left side tiny microgyri connect the ventricle to the normal cortex (asterisk). On the right side the schizencephaly has separated lips, causing an open connection between the lateral ventricle and the convexity of the brai...
Scheme of normal and polymicrogyric cortex

On the right side a schematic representation of 4-layered polymicrogyric cortex. Note that the undulating surface of layer 2 is not wound around visible sulci as in the normal cortex, lending the surface a smooth or crenated aspec...

Schizencephaly has been increasingly recognized in vivo due to the progressive refinement of neuroimaging techniques (07; 46; 05; 06). Although first-generation MR scanners did not achieve sufficient resolution to differentiate polymicrogyria from pachygyria, improvements have made this possible, and indeed imperative for a definite diagnosis.

Sometimes full-thickness defects without polymicrogyria bordering the defect but with associated cortical malformation distant from the defect are classified as schizencephaly (57). In this way the definition, especially of type 2, sometimes tends to become overstretched.

Genetic studies initially focused on EMX2, a homeobox gene, which could not be confirmed (27). Genetic, neuroradiological, and experimental studies have given ground to the vascular origin (fetal cerebral artery occlusion) as the most common etiology (54). The most frequent genetic mutation, usually de novo, associated with schizencephaly, particularly with arterial occlusive or hemorrhagic infarcts, is of the COL4A1 gene (70; 91; 01; 18; 54; 89). Because this mutation primarily involves endothelium of blood vessels, not only is the nervous system a target, but multiple organs might be affected and develop malformations. Congenital cataracts are seen in some patients.

Clinical manifestations

Presentation and course

In nearly all patients affected by schizencephaly, the main clinical manifestations are motor deficits, (usually spastic hemiparesis or diparesis), intellectual and cognitive deficits mental retardation of various degrees, and epileptic seizures (12). Some patients are not epileptic, however, or may show only subclinical paroxysmal activity in the EEG. Organization of the motor cortex may be disrupted and can be shown by transcranial magnetic stimulation and diffusion tensor imaging (04). Hemiparkinsonism was reported in one patient (90). Schizophrenia or psychosis is rare but is reported (100). However, the clinical outcome may be markedly different in different patients, and it is related to type, location, and size of the clefts as well as the presence of associated brain malformations (07; 35; 38; 78; 24; 67).

Schizencephalies may be unilateral or bilateral and closed-lipped or open-lipped, and they may present as isolated malformations or be associated with other structural brain abnormalities such as agenesis of corpus callosum and septum pellucidum, which may even be neurologically asymptomatic in some patients (32; 02). Rare cases of schizencephaly are associated with frontoethmoidal or occipital encephalocele (97; 50). Schizencephaly may be 1-sided with a normal opposite hemisphere, or with focal contralateral polymicrogyria without cleft. Schizencephaly may also be part of more complex malformations (in the case of septo-optic dysplasia, for example) (73; 11). They may be isolated or associated with other supratentorial (polymicrogyria, agenesis of corpus callosum and septum pellucidum) or infratentorial brain abnormalities, such as cerebellar clefts (82), or also may present as part of more complex malformations, such as septo-optic dysplasia (SOD) (73; 69; 12).

Left prerolandic schizencephaly (MRI)

The cleft is lined by polymicrogyric cortex. (Contributed by Dr. Giorgio Battaglia.)

Obviously, patients with large bilateral open-lip clefts or septo-optic dysplasia are characterized by the more severe clinical pictures, whereas those with small, unilateral closed-lip clefts display the mildest clinical signs (21; 69).

Several cases have been reported with syndromic associations (eg, LEOPARD syndrome) (66), Prune belly syndrome, and Nijmegen breakage syndrome (95). A note of caution should be added in the cases where hydrocephalus coexists with open lips connecting the arachnoid space and the lateral ventricle. Infolding of the cortex towards the ventricle may falsely suggest an appearance of a seam lined by abnormal cortex, especially when the resolution of the images is less than optimal to detect polymicrogyria.

Patients with bilateral schizencephaly, particularly if open-lipped, may present with unilateral or bilateral congenital hemiparesis, severe hypotonia, and developmental delay (24; 106) or develop spastic diparesis, often associated with microcephalia and other neurologic deficits such as apraxia and pseudobulbar paralysis. Mental retardation and delay in language development are associated findings, particularly when more cerebral lobes are involved (78). In addition, progressive obstructive hydrocephalus may develop during the first months of life (78).

In patients with unilateral clefts, motor deficits are frequently present on the side contralateral to the cleft. They range in severity from mild asymmetry of motor skills to spastic hemiparesis. Bilateral motor deficits have been reported in few patients, likely related to the presence of cortical dysgeneses contralateral to the cleft. The mental abilities are usually normal in patients with unilateral closed or small open cleft, whereas mental retardation is common in patients with larger clefts (45). Delay in language development and dissociative language representation in the cortex are also related to the presence of open clefts, fronto-parietal location, and extent of the malformation, rather than to the side of the schizencephaly (78; 24; 60).

Analysis of cortical functions has been reported in a few patients with unilateral schizencephaly. Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation have demonstrated that the unaffected motor cortex innervates both hand muscles, thus, indicating functional reorganization of the motor areas in patients with schizencephaly (64; 101; 56; 04). In an asymptomatic patient with left frontal schizencephaly, fMRI revealed activation of the dysgenetic cortex lining the cleft, suggesting a contribution of the malformed cortex in physiologic cerebral functions (92). Another fMRI study in an adult with one-sided full thickness schizencephaly and adult-onset dystonia in the affected half of the body showed activation in the abnormal cortex surrounding the cleft on attempted movement of the contralateral limbs (104). The authors also suggested a role for neuromodulation by transcranial magnetic stimulation to suppress abnormal activity of the area surrounding the cleft.

Focal epilepsy is a frequent finding in both unilateral and bilateral cases. It is present in about half of the cases, and it is refractory to antiepileptic drugs in about a third (35; 58). Bilateral schizencephaly is a higher risk of seizures than unilateral forms (58). In all patients, seizures are mostly focal, and their semeiology is related to the cleft location (36; 16). Focal temporal lobe seizures were precipitated by intermittent photic stimulation during an EEG recording in a 12-year-old boy with schizencephaly and pachygyria (13).

Though onset of epilepsy is usually in infancy or early childhood, rarely some patients may not develop seizures until adult life (09; 61). Schizencephaly was first discovered during the evaluation of seizures during labor in a woman in her late 30s (80). Psychiatric presentations, including psychosis can disclose schizencephaly on brain imaging, as in the case of a 50-year-old man (79).

Infantile spasms, myoclonic seizures, or atonic seizures are rarely reported. The presence and severity of epilepsy is not necessarily related to the severity of the anatomical malformation (36; 24). Seizures may be the presenting symptom in patients with unilateral cleft with mild or no neurologic deficits (36; 21). Even in patients with refractory seizures, epilepsy is not usually characterized by a malignant course, affecting the neurodevelopmental outcome (36; 78; 24). A rare form of seizures, focal hypsarrhythmia with clusters of epileptic spasms, was seen in a group of 12 patients, including 11 with severe focal developmental lesions of which two had open lip schizencephaly (17). Surgery should be seriously considered in this group.

Prognosis and complications

The prognosis depends on the size and extent of schizencephaly and on the presence and location of associated cerebral dysgeneses. In the case of a pathogenic COL4A1 mutation, vascular complications in later life may occur. Clinical manifestations include seizures, cerebral palsy, and intellectual impairment. Patients with bilateral cleft and associated complex brain malformations can be severely handicapped in everyday life. Progressive obstructive hydrocephalus in open-lip schizencephaly may require ventriculoperitoneal shunt (78). Epilepsy, when present, is characterized by focal seizures of multiple-type, which can sometimes be difficult to control (38). By contrast, patients with a single fused cleft have minor motor deficits and normal mental abilities and can lead a normal social life. Epilepsy is often the main clinical problem because focal seizures are resistant to treatment in about one third of the cases (07; 35; 38). A lesion on one side may be functionally compensated by ipsilateral innervation from the unaffected cortex in unilateral schizencephaly (19; 104).

When schizencephaly is caused by COL4A1 mutation, siblings and one of the parents may be affected as well, and medical supervision is advised to cope with the risk of later vascular problems.

Clinical vignette

Case 1. The patient, now 30 years old, was born at term after an uneventful pregnancy and delivery. Motor and mental development were both normal. The clinical history was uneventful until age 22 years when a generalized tonic-clonic seizure occurred during sleep. EEG recordings demonstrated diffuse epileptic abnormalities. The patient was given phenobarbital 50 mg daily for 6 years and had no seizure recurrence. Six months after treatment withdrawal, two convulsive seizures occurred during sleep, preceded by oral automatisms in one case. The treatment with phenobarbital was again started with complete seizure control. A small unilateral open lip schizencephaly in the left temporoparietal region was revealed by MRI.

Left unilateral open-lip cleft in the parietotemporal region (MRI)

The cleft is lined by polymicrogyric cortex; the left lateral ventricle is enlarged and shows a dimple where it communicates with the cleft. (Contributed by Dr. Geoffrey Miller.)

Case 2. The patient, now 8 years old, was adopted at age 2 days. No information on family history or pregnancy was available. The infant was born at term by spontaneous delivery; the weight at birth was 3710 g, and the neonatal general conditions were reported to be good. The early stages of motor development were slightly delayed, and the child was unable to use his right hand. Neurologic examination at age 14 months was characterized by asymmetric spastic diplegia, which was more severe on the right side and also involved the right upper limb. Bilateral schizencephaly (open-lipped on the left and closed-lipped on the right side) associated with absence of septum pellucidum and bilateral thickening of the frontal cortex was demonstrated by MRI.

Bilateral frontal schizencephaly (MRI)

The coronal image shows open-lip left schizencephaly, closed-lip right schizencephaly, the absence of septum pellucidum, and thickened frontal cortex. (Contributed by Dr. Giorgio Battaglia.)

A single convulsive seizure occurred during hyperthermia at age 22 months; no treatment was given, and no further seizures occurred despite the presence of high incidence EEG interictal epileptic abnormalities.

Interictal epileptic abnormalities in bilateral frontal schizencephaly (EEG)

Diffuse discharges of irregular sharp and slow wave complexes are more evident on the anterior leads. The interictal activity is often of larger amplitude on the left side (boxed area). (Contributed by Dr. Giorgio Battaglia.)

Kinesitherapy produced a positive effect on motor skills; the boy is now able to reach the standing position and walk with assistance. General intelligence quotient, assessed by the Griffith Scale (with exclusion of locomotor scale) at age 8.4 years was 76, equivalent to that of a 6.4-year-old child.

Case 3. This boy presented with left arm paresis at the age of 4 months. The pregnancy was complicated by attempted abortion with an unidentified drug in the third month of gestation. When presenting to the pediatric neurologist at 11 years of age, he had spastic monoparesis of the left arm. Otherwise, his behavior and motor performance were normal. On psychological testing he had low normal intelligence. He had no clinical signs of epilepsy. MR of the head showed right-sided neocortical dysplasia with polymicrogyria involving the central motor region and large adjacent area of the frontal lobe. Schizencephaly appeared open at the outside but closed near the ventricle.

11-year-old boy with left-sided schizencephaly bordered by dysplastic cortex (MRI)

The lesion appears open at the outside, but is closed where it reaches the ependyma. (Contributed by Peter G Barth MD.)
11-year-old boy with left-sided schizencephaly (MRI)

Section above the defect shows widespread polymicrogyria. Note the perpendicular strokes of gray cortical matter without intervening sulci. (Contributed by Peter G Barth MD.)
11-year-old boy with left-sided schizencephaly (sagittal MRI)

This section localizes the defect in the central motor zone with additional patches of polymicrogyria advancing in the premotor left frontal lobe region. (Contributed by Peter G Barth MD.)

Biological basis

Etiology and pathogenesis

Schizencephaly is a transmantle defect of one or both cerebral hemispheres, lined by dysplastic polymicrogyric cortex. Some earlier theories held that schizencephaly is secondary to hypoperfusion or ischemic cortical injury; however, other gestational causes such as infections, toxic agents, or trauma have been considered as possible relevant causes (23; 08; 26; 07; 49; 42).

A vascular etiology for schizencephaly and porencephaly has been established, linking both disorders. Ipsilateral absence of the middle cerebral artery has been observed in two of three cases of schizencephaly studied by MRI and magnetic resonance angiography (28). Gould and colleagues discovered a mutation in the Col4A1 gene in a mouse mutant with perinatal hemorrhage and porencephaly (33). The same mutation also occurs in humans (70; 91; 01; 18; 54; 89). Electron microscopic study showed an abnormal structure of the vascular basement membrane, explaining the tendency to hemorrhage or thrombosis. Human cases of COL4A1 mutations also are associated with schizencephaly (18; 89; 103; 105). Pathogenic monoallelic mutations of the human homologue, COL4A1, were subsequently found in several families with recurrent porencephaly by the same group. COL4A1 mutations were also found to underlie cases of familial schizencephaly and porencephaly in a larger study by Yoneda and colleagues (109). Of 61 patients with porencephaly, 15 were found to carry a monoallelic mutation in COL4A1. Of 10 patients with schizencephaly, five carried a mutation. Both de novo and familial cases were identified. Variable findings included hemolytic anemia, optic atrophy, and elevated creatine kinase. Chromosomopathies are not usually described in schizencephaly, but deletion of 22q13.32 was reported in one case who also had an occipital encephalocele (50), and an 8p23.1 microdeletion in a fetus with partial callosal agenesis and schizencephaly was reported (20). Mutations in α- and β-tubulin encoding genes, tubulin being a microtubule-associated protein, involve differentiating neuroblasts even when first expressing neuronal cellular lineage and can generate a spectrum of brain malformations including agenesis of the forebrain commissures and schizencephaly (84). Contactin-associated protein with two genetic mutations is reported in one patient with bilateral schizencephaly (85).

Porencephaly resembling or associated with schizencephaly is usually due to middle cerebral arterial occlusion during the second trimester of fetal life, but venous anomalies related to a poorly formed great vein of Galen, persistent falcine sinus, and cerebral venous thrombosis also are reported (105; 94).

A large epidemiologic study by Curry and colleagues in California involved more than 4 million births from 1985 to 2001, giving a population prevalence of 1.54/100,000 (22). Young parental age and monozygotic twinning were risk factors. Associated anomalies pointing to vascular disruption were found, including gastroschisis, bowel atresias, and amniotic band disruption. A possible role for prenatal use of cocaine or other street drugs is documented by the study of Dominguez and colleagues (26).

Heterozygous mutations of the homeobox gene EMX2 have been reported in a few schizencephaly patients (15; 27; 37). However, EMX2 screening of larger cohorts of patients affected by schizencephaly revealed no pathologic EMX2 mutations (38; 98; 72).

Septo-optic dysplasia (de Morsier syndrome, SOD, OMIM 182230) is a heterogenous congenital malformation complex. Its diagnosis requires the combined presence of two of three congenital defects: (1) optic nerve hypoplasia, (2) pituitary hypofunction, and (3) midline brain abnormalities, typically dysgenesis of the septum pellucidum or corpus callosum (03; 12; 32). In a series of 17 patients with septo-optic dysplasia who were evaluated by MRI, only three had schizencephaly (03); nevertheless, septo-optic-pituitary dysplasia remains one of the strongest associated malformations with schizencephaly and may also involve hypoplasia of the olfactory bulbs and tracts (88; 12; 10; 68). Septo-optic dysplasia with schizencephaly has been called “septo-optic dysplasia plus syndrome” (43). For more information, see the article “Septo-optic-pituitary dysplasia” in Medlink neurology. HESX1 and SOX2 genes, previously associated with septo-optic dysplasia, were tested in a large cohort of 75 schizencephaly patients, including open and closed types, with negative results (71). No pathogenic mutations were found. Two unrelated cases of schizencephaly in young female infants were associated with thrombophilia caused by mutations in the genes for methyltetrahydrofolate reductase and factor V Leiden (39). Hereditary hemorrhagic telangiectasia with schizencephaly has been reported (31).

Schizencephaly is determined by impairment during brain ontogenesis of the mechanisms that govern neuroblast migration and cortical organization. Ischemic cortical injuries and infective agents have been considered as causative factors. Polymicrogyria is present in about half of the affected patients within or adjacent to the schizencephalic clefts (46). This finding supports the hypothesis that both polymicrogyria and schizencephaly may be caused by cortical ischemic damage (08; 07). Polymicrogyria consists of small irregular gyri without sulci or with sulci bridged by fusion of the overlying molecular layer (30). It is believed to arise in some cases from cortical ischemic necrosis primarily affecting the fifth cortical layer (86). Two types of polymicrogyria have been described: (1) the 4-layered type, possibly due to a late second trimester insult (83), and (2) the unlayered type, possibly due to an early second trimester insult (29). Normal cortical lamination also may be seen in some microgyri (93; 51). One of the most important neuropathological features of polymicrogyria not appreciated at the macroscopic resolution of MRI is that the lateral walls of adjacent microgyri often exhibit gaps or discontinuities in the pia mater that result in fusion of their molecular zones (93; 51). This abnormal fusion between gyri may enable synaptic “short circuiting” that could become epileptogenic.

Mild ischemic damage could determine polymicrogyria without cortical infolding, whereas severe and earlier damage deeply involving radial glial fibers could determine a full-thickness cortical cleft lined by unlayered polymicrogyria (07). In addition, transmissible agents may produce schizencephaly, as indicated by the presence of cytomegalovirus DNA and antibodies in two affected children (49). Indeed, full-thickness cerebral clefts can be experimentally induced in hamsters by intraplacental inoculation of Kilham strain of mumps virus (96).

Regarding the neuropathology of schizencephaly, only few classical studies are available (23). The clefts are more frequently located around the Sylvian fissures, but they can also involve the prefrontal and, more rarely, the temporal and occipital lobes. In severe bilateral cases, the descending cortical projections are virtually absent, whereas the striatum is hyperplastic (108). The polymicrogyric cortex surrounding the clefts shows no recognizable layering (62).

In a remarkable study, prenatally diagnosed cases by fetal MRI were compared to MR findings at postnatal follow up (75). Some cases shown to have open lip type schizencephaly had a closed lip appearance of their brains on follow up. The finding adds to the possibility of a fetal disruption in more cases, whether caused by accident or genetic mutation. In another study where the development of the clefts was monitored, the approximation of the clefts and the apparent closure like a zipper was confirmed on intrauterine and postnatal and postnatal follow-up (59). Mechanical factors of incomplete or imperfect closure of the telencephalic flexure may play an important role even in cases of genetically determined etiology (87). This neurodevelopmental dysplasia can be detected and quantitated in the fetus by ultrasonography or fetal MRI (81).

Schizencephaly in the region of the Sylvian fissure is almost universally associated with polymicrogyria in its walls.

Diagnostic workup

Diagnosis rests on neuroimaging. A careful neuroradiologic evaluation of type and extent of the clefts and of associated brain malformations is crucial to the patient assessment, given the correlation between anatomic features and clinical outcome. MRI is the best choice to reveal the cortical cleft lined by gray matter, the cleft extension to the lateral ventricle, and the resultant dimpling of the ventricular walls.

Left unilateral open-lip cleft in the parietotemporal region (MRI)

The cleft is lined by polymicrogyric cortex; the left lateral ventricle is enlarged and shows a dimple where it communicates with the cleft. (Contributed by Dr. Geoffrey Miller.)

MRI also detects the associated malformations, such as agenesis of septum pellucidum and corpus callosum, areas of polymicrogyria adjacent to the cleft or symmetrically located in the contralateral hemisphere (07).

Corpus callosum agenesis (MRI)

Sagittal MRI shows partial agenesis of corpus callosum in a patient with bilateral schizencephaly. (Contributed by Dr. Geoffrey Miller.)

Single photon emission computed tomography and positron emission tomography revealed metabolic activity and perfusion in the walls of the cleft identical to that of normal cerebral cortex (74). Functional MRI studies reported sensorimotor and speech-related activation of the dysgenetic cortex lining the cleft, suggesting a contribution of the malformed cortex in physiologic cerebral functions (92; 52), but the functional relevance of such activation is still debated (101). Diffusion tensor imaging may reveal abnormalities of major fiber tracts in affected patients (56).

CT scan may reveal the gray matter lined cleft. In infants, the malformation should be suspected if CT or ultrasonography reveals corpus callosum agenesis and focal dilatation of the lateral ventricles. Prenatal ultrasonographic diagnosis may be possible in cases with large open clefts or associated with septo-optic dysplasia (77; 48; 81). Prenatal MRI may also differentiate developmental anomalies from destructive lesions (25; 77).

EEG is important because of the high risk of seizures in schizencephaly, and this noninvasive test may reveal potentially epileptogenic foci that are subclinical at the time of the recording.

In the case of schizencephaly, both parents and proband should be genetically screened with COL4A1 mutations in particular to be excluded. The diagnosis sometimes may be made prenatally by fetal MRI or ultrasonography (70; 54; 89).

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Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Harvey B Sarnat MD FRCPC MS

Dr. Sarnat of the University of Calgary has no relevant financial relationships to disclose.
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Former Authors

Geoffrey Miller MD (original author), Giorgio Battaglia MD, Adele Finardi MD, Tiziana Granata MD, and Peter G Barth MD

Patient Profile

Age range of presentation: 0 month to 65+ years
Sex preponderance: male=female
Heredity: heredity may be obtained
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

ICD & OMIM codes

ICD-9: Schizencephaly: 742.4
ICD-10: Other specified congenital malformations of brain: Q04.8
OMIM: Empty Spiracles, Drosophila 2, Homolog of EMX2: *600035

Porencephaly, familial: #175780

Schizencephaly: #269160

Septo-optic dysplasia: #182230

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Schizencephaly

Associated Disorders

Absence of septum pellucidum
Optic nerve hypoplasia
Polymicrogyria

Differential Diagnosis

encephaloclastic porencephaly
hydranencephaly
pachygyria

Also Relevant

Cerebral palsy
Microcephaly
Porencephaly
Septo-optic-pituitary dysplasia complex

Clinical Categories

Developmental Malformations

Schizencephaly …

Schizencephaly

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Special considerations

Pregnancy

Media

References

Contributors

Author

Former Authors

Patient Profile

ICD & OMIM codes

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Also in This Category

Vein of Galen malformations

Epileptic lesions due to malformation of cortical development

Agenesis of the corpus callosum

Epidermal nevus syndromes: neurologic phenotypes

Norrie disease

Aqueductal stenosis

Klippel-Feil syndrome

Cerebellar hypoplasia, dysplasia, and enlargement

Schizencephaly

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Special considerations

Pregnancy

Media

References

Contributors

Author

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Vein of Galen malformations

Epileptic lesions due to malformation of cortical development

Agenesis of the corpus callosum

Epidermal nevus syndromes: neurologic phenotypes

Norrie disease

Aqueductal stenosis

Klippel-Feil syndrome

Cerebellar hypoplasia, dysplasia, and enlargement

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to access the full version.