Clinical and developmental findings in children with giant interhemispheric cysts and dysgenesis of the corpus callosum

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Clinical and Developmental Findings in Children With Giant Interhemispheric Cysts and Dysgenesis of the Corpus Callosum May L. Griebel, MD**, Jane P. Williams, PhD*, Susan S. Russell, MS*, G. T. Spence, MEd*, and Charles M. Glasier, MD** Giant interhemispheric cysts in association with dysgenesis of the corpus cailosum are rare. Clinical and developmental data concerning affected patients are limited, the pathologic basis for these cysts has not been established, and prognosis is uncertain. The purpose of our study was to describe the clinical and developmental findings for 11 children with giant interhemispheric cysts, dysgenesis of the corpus callosum, and ventricular dilatation. Eight of the children required ventricuioperitoneal shunting, eight had normal neurologic examinations, and seven had experienced seizures. Seizure control appeared to correlate with neurodevelopmental function. Cognitively, children ranged from the average to mildly/moderately retarded level. Language delays were frequent, particularly in children with predominantly left hemispheric cysts. Adaptive behavior was mildly delayed with weakness observed in motor skills. Despite the striking neuroimaging abnormalities, our findings suggest the possibility of only mildly delayed neurodevelopmental outcome is good for children with this constellation of neurologic anomalies. Griebel ML, Williams JP, Russell SS, Spence GT, Glasier CM. Clinical and developmental findings in children with giant interhemispheric cysts and dysgenesis of the corpus callosum. Pediatr Neurol 1995; 13:119-124.

Introduction Giant interhemispheric cysts in association with dysgenesis of the corpus callosum have been described since the 1930s [1]. However, these cysts occur rarely, and limited clinical and developmental data about affected pa-

From the Departmentsof *Pediatrics,*Neurology,and *Radiology; Universityof Arkansas for Medical Sciences;Little Rock, Arkansas.

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tients are available in the literature. Approximately 23% of patients with agenesis of the corpus callosum have intracranial cysts of all types; however, interhemispheric cysts occur in fewer than 7% of the patients [2]. A variety of midline cystic lesions has been described, including cysts associated with holoprosencephaly (congenital midline porencephaly), "diencephalic cysts" representing cystic dilatation of the third ventricle in association with agenesis of the corpus callosum, parasagittal arachnoid cysts with intact corpus callosum, porencephalic cysts, intradural interhemispheric cysts, and true interhemispheric cysts with dysgenesis of the corpus callosum [3[. The pathologenetic basis of interhemispheric cysts has not been identified. Analysis of surgical and autopsy specimens has revealed some cysts lined with ependyma and choroid plexus while other cysts are lined with astrocytes, indicating a neuroepithelial origin [2,4,5]. Still other cysts are intra-arachnoid with the inner and outer walls formed by the arachnoid membrane [6]. Developmental outcome appears to be quite variable. In one report of five patients with absence of the corpus callosum, a large interhemispheric cyst, and ventricular dilatation, all had moderate to severe mental retardation, motor deficits, abnormal neonatal development, and seizures [7]. Schwartz and Ghatak [2] reported an infant with profound mental and motor retardation whose postmortem examination indicated polygyria, total absence of the corpus callosum, a large cyst of the interhemispheric fissure which communicated with the lateral ventricle, a collapsed third ventricle, and a reduced aqueduct. This child had congenital hydrocephalus and intractable seizures. Diebler and Dulac [8] found severe mental retardation in 5 patients, moderate mental retardation in 10 patients, and absence of mental retardation in 7 patients with interhemi-

Communicationsshould be addressedto: Dr. Griebel; Universityof Arkansas for Medical Sciences;Department of Pediatrics; 1201 Bishop;Little Rock, AR 72202. ReceivedApril 24, 1995;acceptedJuly 5, 1995.

Griebel et al: InterhemisphericCysts 119

spheric cysts and agenesis of the corpus callosum. Clinical signs were generally limited to isolated macrocrania. In contrast, Mori [3] reported 4 patients with interhemispheric cysts and agenesis of the corpus callosum, including 1 adult, whose developmental outcomes appeared to be positive. One child was described as having slight psychomotor retardation although complete neurodevelopmental evaluations were not reported. Individual cases of neurologically asymptomatic adults, who came to medical attention only because of new onset seizures or headaches, have been described [2,5,7]. Pascual-Castroviejo et al. [9] mentioned 9 patients with interhemispheric cysts in discussing childhood arachnoid cysts, but developmental outcomes were not detailed for the various cyst locations. In addition, it was unclear how many of the patients had dysgenesis of the corpus callosum. Aicardi and Bauman [10] reported 2 children with normal developmental quotients but described their cysts as parasagittal in location. Presence or absence of the corpus callosum was not reported. The purpose of our study was to describe the clinical and developmental outcomes of 11 children with giant interhemispheric cysts associated with dysgenesis of the corpus callosum, the largest series of such patients with complete neurodevelopmental assessments. As the prognosis for these children is uncertain, clinical and developmental findings based on neuroimaging and behavioral evaluations appear critical. Methods Eleven children with giant interhemispheric cysts associated with dysgenesis of the corpus callosum were identified from hospital radiology files for a 5-year period. These children, 2 females and 9 males, ranged in age from 5 months to 5 years at the time of the initial chart review. Diagnosis of a cystic central nervous system lesion was made prenatally by ultrasound examinations in 5 patients. Four children were diagnosed in infancy when they presented with increasing head circumference. One infant with neonatal sepsis was diagnosed when head ultrasonography was performed as part of the initial evaluation. One child was not diagnosed until he presented with seizures at 4 years of age. At the time of the psychological and language assessments, the children ranged in age from 15 months to 6 years, 6 months. Children formally evaluated included 2 females and 8 males because 1 child (Patient 11) was not assessed due to parental refusal. Of the children who had established hand dominance, 5 were left hand dominant and 3 were right hand dominant. Racially, 8 children were white, l was AfricanAmerican, and 1 was Asian. Six of the children were involved in early intervention programs including speech and language, occupational, and physical therapy. Two children were in regular school placements without any additional services, and 2 children were not enrolled in any formal early intervention programs. Socioeconomic status (SES), based on Hollingshead Four Factor Theory [ 11], ranged from unskilled laborers and service workers to minor professional and technical workers. The average SES included skilled craftsmen and clerical and sales workers. Procedure. Each child had received a periodic neurologic examination, and supplemental interviews with the patient's primary care pediatrician were conducted for the 2 patients who had not been examined at the hospital in the past year. Neuroimaging studies were reviewed by the same pediatric neuroradiologist who had no knowledge of any child's neurodevelopmental status prior to his assessment. After receiving approval by the Internal Review Board, parental permission for participation in the psychological and language assessments

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was obtained. The children were assessed individually by a psychologist, psychological examiner, and speech/language pathologist. Parents were interviewed concerning adaptive behavior skills, and they received verbal feedback about cognitive, language, and adaptive behavior test resuits. Instruments. The Bayley Scales of Infant Development-Second Edition [12] was administered to assess early cognitive development in children younger than 2 years of age. Results are reported as a Mental Development Index Score (MDI), with a mean score of 100 and standard deviation of + 15. The Stanford-Binet Intelligence Scale-Fourth Edition [13] was administered to measure cognitive development in patients older than 2 years of age. Subtest areas include verbal reasoning, abstract/visual reasoning, quantitative reasoning, and short-term memory. The overall test composite score has a mean of 100 and standard deviation of ± 16, while the mean standard age score for each subtest area is 100. Cognitive scores on the Bayley and Stanford-Binet scales from 90 to 110 are within the average range, 80 to 89 are within the low average range, 70 to 79 are within the borderline range, and below 69 are in the deficient range. The Preschool Language Scale-3 [14] was administered to determine receptive and expressive language skills, and results are reported for auditory comprehension, expressive communication, and total language. Standard scores have a mean of 100 with a standard deviation of +-15. Scores from 85 to 115 are within the average range, 78 to 84 indicate a mild language disorder, 70 to 77 represent a moderate language disorder, and below 69 indicate a severe language disorder. The Vineland Adaptive Behavior Scale [15] was administered to determine developmental levels of adaptive behaviors, and domains measured include communication, daily living skills, socialization, and motor skills. Responses are based on parental report. Standard scores have a mean of 100 with a standard deviation of ± 15. Scores from 85 to t 15 fall within the adequate range, 70 to 84 are in the moderately low range, and below 69 are in the low range.

Results

Neuroimaging. All children underwent computed tomography (n = 2) or magnetic resonance imaging (n = 9), which confirmed the presence of a large interhemispheric cyst associated with dysgenesis of the corpus cap losum (Table 1). All children had some degree of ventricular dilatation, often with colpocephaly, although not all developed signs of obstructive hydrocephalus. Five children had no evidence of anomalies other than a large interhemispheric cyst, dysgenesis of the corpus callosum, and ventricular dilatation. One child had schizencephaly, while 5 children had other neuronal migration defects including gray matter heterotopias and pachygyria. Patient 9 had the most significant anomalies, including a presumed hamartoma of the tuber cinereum (Figures 1 and 2). Figures 3 and 4 demonstrate the degree of abnormality in Patient 6 who was found to be developmentally normal despite the remarkable magnetic resonance imaging findings. Clinical. Eight of the 11 children required ventriculoperitoneal shunting with shunt revisions performed subsequently in 4 of the 8 children. No shunt infections had occurred. Seven of the 11 children had been diagnosed with seizures. One child had been withdrawn successfully from medication, 3 children were well controlled with antiepileptic therapy, and 3 had poorly controlled seizures. Seizure types were predominantly partial with complex partial seizures, focal motor seizures, or secondarily

Table 1. Neurologic findings in patients with giant interhemispheric cysts and dysgenesis of the corpus canosum

Patient

Age at Diagnosis

Hydrocephalus Requiring Shunt

Shunt Revisions

1

1 Day

Yes

None

2

Prenatal

Yes

3

5 Wks

4

Associated Abnormalities

Seizures

Neurologic Examination

Additional Imaging Findings

Controlled

Hypotonia

Left hemispheric neuronal migration defects

Two

Cleft lip, palate, and tongue; syndactyly; small paipebral fissures; epicanthal folds None

No

Normal

Yes

None

None

Controlled

Normal

Prenatal

No

N/A

None

No

Normal

5

1 Day

Yes

None

None

Mild ataxia and hemiparesis

6

4 Yrs

No

N/A

None

Uncontrolled (history of status epilepticus) Controlled

No neuronal migration defects No neuronal migration defects Left cerebral hemiatrophy; dysgenetic gray matter adjacent to cyst No neuronal migration defects

7

2 Mos

Yes

One

None

Uncontrolled

Normal

8

Prenatal

Yes

Multiple

None

Resolved

Normal

9

3 Mos

Yes

Multiple

Accessory great toe

Uncontrolled

Significant hemiparesis

10

Prenatal

Yes

None

Congenital cytomegalovims

No

Normal

11

Prenatal

No

N/A

None

No

Normal

Normal

Cystic lesion in left periventricular white matter; heterotopias adjacent to cyst No neuronal migration defects Left parietal schizencephaly; heterotopia adjacent to cyst Hamartoma of tuber cinereum; dysgenetic left cerebral hemisphere with pachygyria Punctate dystrophic calcification around 3rd ventricle; right hemispheric neuronal migration defects No neuronal migration defects

Abbreviation: N/A --- Not available

generalized tonic-clonic seizures observed. The child with the tuber cinereum hamartoma also had gelastic seizures. Patient 5 had experienced status epilepticus. Neurological. Eight of the 11 children had normal neurologic examinations including cranial nerves, motor and cerebellar function, reflexes, and gait. Sensory evaluation was limited by age. Patient 5 was described as neurologically and developmentally normal until she developed prolonged focal motor status epilepticus which was recalcitrant to treatment. She was left with a significant hemiparesis which has generally resolved, but she remains neurologicaUy and developmentally mildly abnormal. Cognition. Cognitive testing indicated that 1 child was functioning in the average range of intelligence, 2 were within the low average range, 5 were within the borderline range, 1 was within the mild mental retardation range, and

1 was within the moderate mental retardation range (Table 2). Analysis of group test results on the Standard-Binet Intelligence Scale indicated short-term memory and quantitative reasoning skills were within the low average range while verbal reasoning and abstract visual reasoning skills were within the borderline range. There was a significant difference between the children's higher short-term memory standard age score and lower abstract visual reasoning standard age score (Figure 5) based on a 15% confidence interval [13]. Language. Language testing indicated 2 children with average language development, 1 with mild language disorder, 1 with moderate language disorder, and 6 with severe language disorders (Table 2). Within the receptive language domain, 3 children had average skills, 1 had a mild receptive language delay, 3 had moderate receptive

Griebel et al: Interhemispheric Cysts

121

Figure 1. Patient 9 with shunted hydrocephalus, uncontrolled seizure disorder including gelastic seizures, and right hemiparesis. Sagittal T lweighted (TIC:400 ms, TE: 15 ms) image discloses absence of the corpus callosum, elliptical-shaped mass in the diencephalic region compatible with a hamartoma of the tuber cinereum (black arrows), and large multiloculated interhemispheric cysts with intermediate signal intensity loculation posteriorly (black arrowheads).

Figure 3. Patient 6 underwent magnetic resonance imaging because of new onset seizures. Sagittal Tj-weighted (TR: 400 ms, TE: 17 ms) image discloses absence of the posterior body and splenium of the corpus callosum, hypertrophy of the anterior commissure (black arrow), and loculated interhemispheric cysts with higher signal intensiO, in the posterior portion (white arrows).

results on the Vineland Adaptive Behavior Scale indicated that communication, socialization, and daily living skills were within the moderately low range, while motor skills were within the low range (Figure 6).

delays, and 3 had severe delays. Within the expressive language domain, 3 children had average skills, 2 had moderate expressive delays, and 5 had severe delays. Adaptive Behavior. Adaptive behavior skills indicated 3 children had adequate skills, 3 had moderately low skills, and 4 had low skills (Table 2). Analysis of group test

Giant interhemispheric cysts present a dramatic picture on neuroimaging studies. The clinician and radiologist,

Figure 2. Patient 9: Axial Trweighted (TR: 400 ms, TE: 15 ms) image discloses dysmorphic gray matter adjacent to the posterior cyst loculations in the left cerebral hemisphere (black arrows).

Figure 4. Patient 6: Coronal Tl-weighted (TR: 400 ms, TE: 17 ms) image discloses loculated interhemispheric cysts with higher signal intensity in the posterior portion (white arrows). Multiple gray matter heterotopias appear adjacent to the right posterior cyst loculations (black arrows).

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Discussion

Table 2. Developmental findings for patients with interhemispheric cysts and dysgenesis of the corpus callosum Age (yrs, mos)

Patient

Adaptive Behavior

Handedness

Sex

IQ Composite Borderline (SS = 69) Borderline (SS = 75) Borderline (SS = 73) Borderline (SS = 78) Mild mental retardation (SS = 68) Low average (SS = 88) Borderline (SS = 69) Average (SS = 96) Moderate mental retardation (SS = 46) Low average (SS = 82)

1

1, 3

R

F

2

2, 7

N/A

M

3

3, 8

N/A

M

4

3, 8

L

M

5

4, 8

L

F

6

5, 1

R

M

7

5, 4

L

M

8

5, 10

L

M

9

5, 10

L

M

10

6, 6

R

M

Abbreviations: L = Left N/A = Not available

Language Composite Average (SS = 95) Mild delay (SS = 83) Severe delay (SS = 59) Severe delay (SS = 68) Moderate delay (SS = 70) Average (SS = 88) Severe delay (SS = 63) Severe delay (SS = 69) Severe delay (SS = 50) Severe delay (SS = 66)

Composite Adequate (SS = 86) Moderately low (SS = 76) Low (SS = 55) Moderately low (SS = 75) Moderately low (SS = 73) Adequate (SS = 89) Low (SS = 66) Low (SS = 64) Low (SS = 44) Adequate (SS = 85)

R = Right SS = Standard score

asked to prognosticate long-term developmental outcome, may erroneously state that the prognosis is dismal for neurodevelopmental functioning in these patients. In fact, most of the patients in this study had been given negative predictions for the children's long-range status. The children in our population demonstrate the difficulty one has in predicting function from structure. Although the child with the most severe intracranial anomalies was the most delayed, the child with a massive cyst and gray matter heterotopias scored within the low average to average range on all neurodevelopmental measures. Of the 5 subjects with no anomalies except for the cyst and dysgenesis of the corpus callosum, 2 children performed within the borderline range and had significantly delayed language, 1 child scored within the borderline range and

had mild language delay, and 1 child performed within the mild range of mental retardation with moderate language delay. Unfortunately, 1 child with no additional anomalies, whose parents refused to allow testing, was not formally evaluated. He had been reported to have met all developmental milestones including speech. The need for ventriculoperitoneal shunting did not strictly predict developmental outcome, nor was performance uniformly affected even by multiple shunt revisions. The child who demonstrated the highest overall scores on neurodevelopmental testing did not require a shunt, nor did the child who had a normal neurologic examination and had met normal developmental milestones. Yet, the only other child in the group without a shunt had borderline delay.

90

Low Average 8O

8

Borderllne

[] Figure 5. Mean standard age scores for subtests from the Stanford-Binet Intelligence Scale-Fourth Edition.

70 Mild Delay 6O

!

I

!

I

P

Griebel et al: Interhemispheric Cysts

123

115

Adequate

85

•

)

•

Figure 6. Mean standard scores for domains on the Vineland Adaptive Behavior Scale.

Moderately LOW • 70

--

low i

I

I

I

!

o~ o~

The one factor that did correlate with neurodevelopmental function was the presence of intractable epilepsy. The 3 children with uncontrolled seizures demonstrated the greatest cognitive delays. The only child to have experienced deterioration in neurologic and developmental status was the patient who suffered status epilepticus for more than 4 hours, Seizure control was poorest in the child who had the greatest number of central nervous system anomalies on neuroimaging and daily seizures despite multiple medication regimens. Overall, children in this study were found to exhibit wide variability in cognitive function ranging from average to moderately mentally retarded. Relative strengths were observed in short-term memory skills and quantitative reasoning which were within the low average range. Relative weakness was documented in visual abstract reasoning skills which were within the borderline range. A striking number of the children were left hand dominant and had significant language delays. Although not all of the children had established hand dominance, 4 children with severe language delays had predominantly left hemispheric cysts and were left handed, suggesting the possibility of reorganization of language function. No child with a predominantly left hemispheric cyst location or with bilateral cysts had normal language development. The children demonstrated mild delays in adaptive behavior skills. Relative weakness was indicated in motor skills. Delays in acquisition of motor skills appeared to have had a negative impact on daily living skills which require fine motor coordination. Although 8 children in our study had normal neurologic examinations and had generally met early developmental milestones by parental report, our findings suggest the need for comprehensive developmental assessments in these children. Early intervention, especially speech and language therapy for children with predominantly left hemispheric cysts, may be indicated. Our findings suggest that the prognosis for only mildly delayed neurodevelop-

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mental outcome is good for children with giant interhemispheric cysts and dysgenesis of the corpus callosum, despite the striking imaging abnormalities. The authors thank Nettie A. Koshoffer for assistance with computer graphics. References [1] Zingesser L, Schechter M, Gonatas N, Levy A, Wisoff H. Agenesis of the corpus callosum associated with an interhemispheric arachnoid cyst, Br J Radiol 1964;37:905-9. [2] Schwartz AM, Ghatak NR. Interhemispheric cysts in association with agenesis of the corpus callosum. Clin Neuropathol 1990;9:17780. [3] Mori K. Giant interhemispheric cysts associated with agenesis of the corpus callosum. J Neurosurg 1992;76:224-30. [4] Kameyama S, Kuroki M, Toyama M, Watanabe M, Kaneko HK. lnterhemispheric epithelial cyst. Surg Neurol 1988;30:391-5. [5] Solt LC, Deck JHN, Baim RS, TerBrugge K. lnterhemispheric cyst of neuroepithelial origin in association with partial agenesis of the corpus callosum. J Neurosurg 1980;52:399-403. [6] Coffey RJ, Lunsford LD. Supracallosal interhemispheric arachnoid cyst: Resolution after intracystic hemorrhage and infection. Surg Neurol 1988;29:153-8. [7] Swett HA, Nixon GW. Agenesis of the corpus callosum with interhemispheric cyst. Pediatr Radiol 1975;114:641-5. [8] Diebler C, Dulac O. Cerebral and cranial malformations. In: Diebler C, Dulac O, eds. Pediatric neurology and neuroradiology. New York: Springer-Verlag, 1987:1-16. [9] Pascual-Castroviejo I, Roche MC, Bermejo AM, Arcas J, Blazquez MG. Primary intracranial arachnoidal cysts. Childs Nerv Syst 1991 ;7:257-63. [101 Aicardi J, Bauman F. Supratentorial extracerebral cysts in infants and children. J Neurol Neurosurg Psychiatry 1975;38:57-68. [11] Itollingshead AB. Four factor index of social status. New Haven: Author, 1975. [12] Bayley N. Bayley scales of infant development. 2nd ed. Orlando: The Psychological Corporation, 1993. [13] Thorndike RL, Hagen EP, Sattler JM. The Stanford-Binet intelligence scale. 4th ed. Chicago: Riverside Publishing Company, 1986. It41 Zimmerman IL, Steiner VG, Pond RE. Preschool language scale-3. San Antonio: The Psychological Corporation, 1992. [15] Sparrow SS, Balla DA, Cicchetti DV. Vineland adaptive behavior scales. Circle Pines, MN: American Guidance Service, 1984.