Friday, November 9, 2012
Schizencephaly is a development disorder characterized by abnormal clefts in the cerebral hemispheres (NINDS publication). Some scientists deem it to be a most severe, yet restricted, of the cortical malformations (Volpe, 1995).
The pathology of this disorder shows that the cleft may be narrow or closed or wide and open. The cleft is usually located near the precentral or postcentral gyri, they can be unilateral (occurring on only one side) or bilateral (occurring on both sides). Multiple small convolutions in the malformed brain, or polymicrogyria, have been noted. Other malformations included or usually noted with this disorder are microcephaly (small brain),
gray matter heterotopia (absence of binocular equilibrium in the eyes), dysplasia (abnormal tissue development) and hypoplasia (tissue underdevelopment) (Carson, 1996).
It has been deemed a cephalic disorder (by NINDS), congenital neurologic malformation (Icenogle & Kaplan, 1981), or a neuronal migration disorder (Volpe, 1995). All are accurate and basically describe some specific characteristics of the disorder.
As in any discussion of a neurologic disorder, the discussion of its onset is crucial in defining it. There is believed to be a complete agenesis of a portion of the germinative zones and thereby the cerebral wall that leaves the seams or clefts in this anatomical abnormality. This injury in the germinative zones is also deemed to affect the migrating neurons-therefore the notion of neuronal migration disorder. Migrational events in the cerebrum happen in the third month of gestation.
For a better understanding, a brief discussion of ontogenesis-the process of predetermined events occurring in proper sequence to insure normal development of the CNS-is in order. Normal ontogenesis of neural tissue is a complex process that can be divided into three developmental phases: (1) embryogenesis from 0 to 1 month of gestation characterized by induction; (2) cellular proliferation and migration from 1 month gestation to the postnatal
period; and (3) maturation of cellular organization, synaptic development, and myelin formation occurring from 16 weeks' gestation to the fourth year of postnatal life (Icenogle & Kaplan, 1981).
The events during the second phase of normal ontogenesis-cellular proliferation and migration-will be explored further for its pertinence to the topic on hand. By 30 days of gestation with induction completed, cellular differentiation is initiated. Proliferation begins in the ependymal matrix zone. Migration occurs outward from the germinal matrix to the cortical plate, the so-called gray matter, where cells settle and extend lateral cellular processes to form the intermediate zone, or white matter. All migrations occur in an inside-to-out fashion, with the earliest arrivals closest to the center. This phase leads to the development of the cerebellum, cerebrum, brain stem, or commissural elements.
Consequences for the disorder - ecological consequences:
The neurological manifestations of schizencephaly include infantile hypotonia, seizure disorder, developmental delay, mental retardation, microcephaly, and motor dysfunction (spastic quadriplegia, hemiparesis, hypotonia). In several literatures that discuss schizencephaly, they emphasized the rarity of it and only knew about it from autopsies of infants who died because of failure to thrive. However, because of technological imaging advances (discussed further in this paper below) the clinical spectrum was discovered to be broader than previously expected. Severity relates to extent and distribution of cerebral involvement (See Table 1).
The ecological consequences of schizencephalic patients are the same as with other structural abnormalities. According to Spreen, Risser, & Edgell (1995), a general finding is the strong association between malformations, on the one hand, and impaired development of brain and intellect, on the other. The studies also found more left-handedness in these children and concluded that a reorganization of the hemispheric specialization takes
place. However, such a reorganization is "brittle" and tends to lead to a cognitive decline, particularly if the number of shunt revisions in left-handers is taken into account (Spreen, Risser, & Edgell, 1995). In a review of studies it was stressed that although a variety of cognitive and perceptual-motor deficits are frequently found, there is "no common
neuropsychological pattern" (Bigler, 1988) and little systematic relationship between ventricular size and type and degree of psychological impairment can be shown.
Table1: Schizencephaly: Anatomical (MRI) and Clinical Features
Closed clefts 50%
Parietal, temporal or occipital 26%
Associated septo-optic dysplasia 25%
Not frontal 29%
Open lip 94%
Closed lip 22%
--from Volpe, J (1995). "Neurology of the Newborn" 3rd ed.
There is debate about the association between minor physical anomalies and the development of intelligence and occurrence of behavior problems. Rappoport and Quinn (1975) found that attractiveness has no relation to the minor physical anomaly, so that a direct influence on social interaction with peers is unlikely. Hyperactive, disruptive and impulsive behavior has been reported to be associated with the number of minor anomalies in school-aged boys. In girls, passivity, low activity level, withdrawal, and chronic anxiety were found to be associated with the minor anomalies.
Anomaly scores were also negatively correlated with IQ (Waldrop and Goering 1971, Waldrop et al. 1976). Overall, long-term follow-up shows high infant mortality and severe impairment in structural malformation disorders, whereas a few produce little evidence of overt impairment. Although some improvement of mental functions during childhood has been noted, long-term mental development is frequently limited. Behavioral problems and specific patterns on speech arise probably as the result of the need for intensive handling and hospitalization during infancy and the continued need for assistance, especially in children with severe motor impairment.
Test procedures to evaluate the disorder:
Computerized Tomography (CT) scan, ultrasonogram and Magnetic Resonance Imaging (MRI) are the instruments used to detect this anomaly. In fact, the advent of the MRI greatly expanded understanding of anatomical and clinical aspects of schizencephaly. Previous notions (based solely on autopsied cases) point that schizencephaly is rare, bilateral, and associated invariably with severe neurological deficits. These notions are, now deemed
A publication by Brown et. al. (1993) reported neuropsychological, MRI, electroencephalographic telemetry, and sodium amytal test findings of a 32-year-old, left handed man with unilateral left hemisphere schizencephaly (presented as Case 3 later). The neuropsychological tests administered were: Information (WAIS-R), Controlled Oral Word Association Test, Boston Naming Test, Arithmetic (WAIS-R), Written language sample, Oral reading, Proverb Interpretation (spontaneous and multiple choice), Similarities (WAIS-R), Rey-Osterreith Figure, Block Design (WAIS-R), Judgment of line orientation, design fluency, Mazes (WISC-R), Logical memory passage (immediate and delayed), Visuographic memory (immediate and delayed).
Techniques for remediation/compensation:
Briefly, for motor disorders the remediation for this is occupational and physical therapies; for cognitive issues, early intervention programs are in place; finally for seizure disorders
medications are used to control and alleviate them. Additionally, regular neuropsychology/ neurology appointments are needed to further remediation and compensation techniques. I will now cite a couple of case studies to further the discussion.
Case I: Small Open-lip Frontoparietal Schizencephaly
Patient 1 was a boy born to non consanguineous parents after a full-term pregnancy, during the last three months of which intermittent fever occurred. At birth, hepatosplenomegaly (enlargement of both liver and spleen), hyperbilirubinemia (excessive amount of bilirubin in blood), and abnormal liver function were observed. On second day of life, Patient 1 had
a short-term episode of generalized hypertonia. Neurological examination showed pendular nystagmus, strabismus, truncal hypotonia, and right-sided hypertonia. The patient was admitted to the hospital and virological investigations were positive for cytomegalovirus (a herpes-type virus) DNA in the serum, cerebrospinal fluid (CSF), and urine. Patient was treated with ganciclovir regimen. The infant was given foscarnet at a dosage of 60
mg/kg daily for two weeks, followed by a maintenance therapy of 90mg/kg three times weekly for three months. Treatment was successful. At one year of age, the patient had two seizures characterized by generalized hypotonia, and an EEG showing spike-and-wave complexes in the temporoparietal regions, prevailing in the left hemisphere. At neurological examination, microcephaly, pendular nystagmus, generalized hypertonia, and hyperreflexia.
Severe mental retardation was also present (Iannetti, P. et.al, 1998).
Case 2: Schizencephaly Associated With Psychosis
Schizencephaly has not been associated with psychosis in previous reports, but Patient 2 is a case that ties the two. This woman had had several admissions to psychiatric hospitals for either psychotic episodes or depressive states accompanied by suicide attempts. She was born with left sided weakness, reduced vision, and strabismus in her left eye. She had
delayed developmental milestones, received the diagnosis of cerebral palsy at the age of 2, and was subsequently found to be mentally retarded. Seizures started at the age of 7 and she treated with carbamazepine with good effect. She was in and out of the hospitals. The admissions were mainly for depressive symptoms, suicidal ideation, social withdrawal, and
abnormalities of thought processes. By age 18 she was hearing voices. She was given a schizophreniform disorder and treated with neuroleptic drugs. She was treated at different times with therapeutic doses of haloperidol, loxapine, fluphenazine, perphenazine, nortriptyline, sertraline, and benztropine either singly or in combination. Her physical examination showed her having dysarthria, left sided strabismus, brisk reflexes in her
left limbs, and gait disturbances consistent with cerebral palsy. The results of all blood tests, chest radiography, and ECG were within normal limits. Her IQ (on WAIS-R) were 63 for full IQ, performance IQ of 60, and verbal IQ of 67. They were in the mentally retarded range. Her bender gestalt and achievement tests show difficulties in arithmetic and timed
tasks (Alexander, R.C. et. al., 1997).
Case 3: Left Hemisphere Type I Schizencephaly
Patient 3 is a 32-year-old, left-handed man who had two years of college education and was evaluated for medically refractory complex partial seizures that began at age 26 years. The seizures were treated with antiepileptic drugs. He was diagnosed with cerebral palsy at birth when he was noted to have right spastic hemiparesis. He subsequently underwent two
heel cord releases to correct deformities related to spasticity of the right foot and ankle. All development milestones were age appropriate except for ambulation at three years of age. Speech and language development were normal. He owns and manages a successful land surveying business. There is no family history of sistrality, seizures, developmental abnormality, neurological dysfunction, or neuropsychological deficit (Brown, et. al.
The literature for schizencephaly is scant. As pointed earlier, it has been seen as a "rare" disorder. However because of MRI technology, it is more easily diagnosed and seen today. Brown, et. al. (1993) reported that in the particular case of Patient 3, had he not developed epilepsy later in life the schizencephaly would have gone undetected. Most of the literature on schizencephaly are case studies on patients with it. Some interesting research topics associated with schizencephaly that was not covered earlier are those discussing the possible causes of this anomaly. The most cited are viral (cytomegalovirus or CMV) and genetic (homeobox gene EMX2 mutation).
Alexander, R.C., Patkar, A.A., Lapointe, J.S., Flynn, S.W., Honer, W.G.
(1997). Schizencephaly asociated with psychosis. Journal of Neurology,
Neurosurgery and Psychiatry, 63(3), 373-375.
Bigler, E.D. (1988). The neuropsychology of hydrocephalus. Archives of
Clinical Neuropsychology, 3, 81.
Brown, M.C., Levin, B.E., Ramsay, R.E., & Landy, H.J. (1993). Comprehensive
Evaluation of Left Hemisphere Type I Schizencephaly. Archives of Neurology,
Carson, L. (1996). Virtual Hospital: Radiology Resident Case of the Week:
Ianetti, P. et. al. (1998). Cytomegalovirus Infection and Schizencephaly:
Case Reports. Annals of Neurology, 43(1), 123-127.
Icenogle, D.A. & Kaplan, A.M. (1981). A review of congenital neurologic
malformations. Clinical Pediatrics, 20, 565.
National Institute of Neurological Disorders and Stroke (NINDS). Cephalic
Rapoport, J.L. & Quinn, P.O. (1975). Minor physical anomalies (stigmata) and
early developmental deviation: A major biologic subgroup of "hyperactive"
children. International Journal of Mental Health, 4, 29.
Spreen, O., Risser, A.H. & Edgell, D. (1995). Developmental Neuropsychology.
New York: Oxford University Press.
Volpe, J. (1995). Neurology of the Newborn, 3rd ed. Philadelphia: W.B.
Waldrop, M.F. & Goering, J.D. (1971). Hyperactivity and minor physical
anomalies in elementary school children. American Journal of
Orthopsychiatry, 41, 602.