SEPTO-OPTIC DYSPLASIA: THE CLINICAL INSIGNIFICANCE OF AN ABSENT SEPTUM PELLUCIDUM

SEPTO-OPTIC DYSPLASIA: THE CLINICAL INSIGNIFICANCE OF AN ABSENT SEPTUM PELLUCIDUM

Jane William Michael C. Brodskv May Griebel Charles M . Glasier Diana Cald well Phyllis Thomas

Optic nerve hypoplasia is now known to be associated with a broad spectrum of congenital cNS malformations. As originally described by de Morsier in 1956, the term septo-optic dysplasia referred to the triad of optic nerve hypoplasia, absence of the septum pellucidum and agenesis or thinning of the corpus callosum. The clinical association of pituitary dwarfism and other hypo- thalamic-pituitary dysfunction with septo-optic dysplasia was later recognized (Hog et al. 1970). Recent reports of magnetic resonance imaging (MRI) in septo-optic dysplasia have demonstrated cerebral hemispheric abnornialities (schizencephaly) and absence of the pituitary infundibulum (posterior pituitary ectopia, infundibular hypoplasia) as variable components, leading to an expanded definition of septo-optic dysplasia (Kelly el al. 1988, Barkovich et al. 1989, Kaufman et al. 1989, Brodsky et al. 1 990).

Children with septo-optic dysplasia usually have poor vision in both eyes and nystagmus. A subset of these children will appear blind in infancy but subsequently develop a modest degree of vision function, and thereby fall within the spectrum of delayed visual maturation (Fielder and Mayer 1991). The neurodevelopmental prognosis of children with septo-optic dysplasia is controversial. Studies have reported diverse functioning, from normal development to significant

neurodevelopmental delay (Acers 1981, Skarf and Hoyt 1984). Margalith and colleagues (1 984) found a high prevalence of cerebral palsy (57 per cent), mental retardation (71 per cent), epilepsy (37 per cent) and behavior problems (20 per cent) in 51 patients with bilateral optic nerve hypoplasia, although the prevalence of these anomalies in patients with septo- optic dysplasia was not specified and the patient population was biased toward severely affected patients. In a recent neuro-anatomical review of the septum pellucidum, Sarwar (1989) concluded that absence of the septum pellucidum in- variably connotes neurological impairment, and suggested that learning disabilities and mental retardation can be expected with abnormalities of the septum pellucidum.

The function of the septum pellucidum is unclear, probably because of its multiple anatomical connections with subcortical regions (Fried 1972). Animal research has demonstrated that surgical removal may result in performance deficits on spatial reasoning tasks, resulting from either inattention to relevant details or memory loss (Stahl and Ellen 1973). The reduction of spontaneous alternation in rats with septa1 lesions has been attributed to the loss of inhibitory mechanisms (Douglas and Raphelson 1966). Evidence con- cerning the neurodevelopmental con- sequences of congenital absence of the

septum pellucidum in humans is lacking, although a case study involving a blind adolescent with septo-optic dysplasia and endocrine dysfunction revealed a deficit in comprehension of topographical space (Griffiths and Hunt 1984). This patient was significantly less able to learn a floor maze or to trace lines based on kinesthetic cues compared with a blind control. However, her comprehension of static spatial relations on an angle-copying task was intact, which would argue against a n overall defect in spatial cognition. These studies suggest the possibility of problems in learning and responding on spatial tasks when the septum is congenitally absent.

Since the clinical function of the septum pellucidum in humans remains obscure, the present study was designed to examine the neuropsychological functioning of a subset of children with septo-optic dysplasia, whose neuroradiological abnormalities were limited to small anterior visual pathways and absence of the septum pellucidum. It has been our clinical observation that children with optic nerve hypoplasia and absence of the septum pellucidum are usually intelligent and do not demonstrate overt neurological problems unless there are additional M R I abnormalities involving the cerebra I hem is p h er es or pituitary infundibulum (Brodsky 1991). The goal of this study was to evaluate the developmental status of this select group of patients and to determine whether specific neurodevelopmental deficits are consistently associated with an absent septum pellucidum. These findings would be an important step in correlating the overall neurodevelopmental prognosis of specific neuroradiological subgroups in septo-optic dysplasia.

Patients and method Sic bjects Seven children were identified with unilateral or bilateral optic nerve hypoplasia whose neurological abnormalities were limited to absence of the septum pellucidum and abnormal thinning or signal attenuation of one or both prechiasmatic intracranial optic nerves on TI-weighted M R I (Fig. I ) . The patients were selected from a population of 40

Fig. I . Coronal Ti - weighted MR scan dernonsrraiing absence o/ seprunt pellucidurn and hypoplastic [elf opric nenv (small arrow); large arrow denores normal right intracranial opric nerve.

children with , optic nerve hypoplasia. Those with an intact septum pellucidum, or with neuroradiological abnormalities involving the cerebral hemispheres (schizencephaly, cortical heterotopia, encephalomalacia) or pituitary infundibulum (posterior pituitary ec t opia , infundibular hypoplasia) on M R I were excluded. Absence of the septum pellucidum was always complete and, in most cases, was associated with mild ventricular enlargement and variable squaring of the frontal horns. Mild thinning of the corpus callosum was present in three cases (patients I , 3 and 7). All of the children were growing normally and were endocrinologically asymptomatic.

The patients ranged in age from 3 years 9 months to 19 years 2 months. Prenatal history was available for all except one child, who was adopted. Of the other six, five were first-born children. Maternal age ranged from 17 to 23 years, and neonatal jaundice had been present in three of the seven patients. Pregnancy had been complicated by toxemia in one subject. None of the children had been of low birthweight. One mother took isoniazide during her pregnancy due to a positive tuberculin skin test, but no other drug or alcohol use was reported by any of the other mothers.

Measures After obtaining approval from the Internal Review Board, each patient was

In M

491

i

z TABLE I Neuropsychological measurcs administered

Test adminisrered Patients

Intelligence Wechsler Adult lnrtlligence Scale-Revised (WAIS-R) Wechsler intelligence Scale for Children-Revised (WISC-R) Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R) A ehievetiient Wide Range Achievement Test-Revised (WRAT-R) Woodcock-Johnson Psycho-Educational Battery (WJ) Lamuape Bosron h a m i n g Peabody Picture Vocabulary Test-Revised (PPVT-R) Clinical Evaluation of Language Fundamentals-Revised (CELF-R) Exrxessive One-Word Picture Vocabulary Test-Revised (EOWPVT-R) Test for Auditory Comprehension of Language (TACL-R) Test of Language Development-Primary (TOLD-2) Goldman Fristoe Test of .4rticulation (GFTA) Memory Wechsler Memory Scale-Revised (WMS-R) Rey Auditory Verbal Learning Test (RAVLT) Wide Range Assessment of Memory and Learning (WRAML) McCarthy Scales of Children’s Abilities (Memory subtests) Visual Sparial Judgement of Line Orientation Visual Form Discrimination Test Motor-Free Visual Perception Test (MVPT) Block Design Subtest (WISC-R) Visual-Motor Integration Rey-Osterrierh Complex Figure Drawing Beery Visual-Motor integration Test (VMI) Sensory/Perceptual/Motor Skills Reitan-Klove Sensory-Perceptual Exam Finger-Tapping, Grip-Strength, Grooved Pegboard E.cecutive Ainciioning Wisconsin Card-Sorting Test (WCST) Trail Making Test (Parts A and B) Continuous Performance Test (CPT) Behavior/Personality Minnesota Multiphasic Personality Inventory (MMPI) Child Behavior Checklist (CBCL) Conners Parent Rating Scale (CPRS) Vineland Adaptive Behavior Scales (VABS) ELyr- . 3

evaluated by an ophthalmologist, neur- ologist, psychological examiner, speech- language pathologist and neuropsychol- ogist . The ophthalmological examination included assessment of visual acuity, evaluation for an afferent pupillary defect, determination of the presence or absence of nystagmus, assessment of visual fields when possible,‘and examination of optic disc and retina. The neurological examination involved assessment of cranial nerves, motor function, sensory function, co-ordination and reflexes. The neuropsychological and speechllanguage

492 evaluations involved assessment of

intelligence, achievement, language, memory, visual spatial skills, visual- motor integration, motor skills, psychomotor strength and speed, sensory- perceptual intactness, executive functioning and behavior/personality. The specific neuropsychological and language tests administered to each patient are listed in Table I . Tests were modified as needed for visual difficulties.

Results Neuro-ophthulniological exuminatiort Four of the patients had nystagmus. Optic nerve hypoplasia was unilateral in three

- 2 TABLE I I

Patient characteristics La- '' . _I_ o\

0 -z

- Normal 19.2 F L-NO Ilghl perception

K--20 20

I?:J hl L-?0/?0 R-Light

perception

6:9 F L-?0/11)0 K--?OI100

J:8 F L-20/150 R--ZO/2OO

2:9 hl L-?0/200 R-20/90

3.1 h1 L-Light percepiion

R-?0/30

- Normal

+ Normal. exccpi lo r gross motor skills

+ Normal

+ Normal. excepi for g r o s mo[or thills

+ Normal, cxcepi for gro$, motor tkil ls

- Normdl

Average Low-average to Borderline to 0'

PIQ= I12 Sh to 73id anti le D FSlQ = 102 2

Superior Abo\c-average Superior P $

VlQ=91 average average

VIQ = 122 PIQ= 126 FSIQ= 126

Index :: I30

High-arerage Aboke-xcrage High-aberagc Index = I19 VIQ = I I Y

PIQ= 109 FSlQ = I17

Low average V l Q = 87

FSIQ = 84 hli ldly delaycd

VIQ=66 PIQ = 65 FSlQ = 62

Low-average VIQ=86 PIQ=81 FSlQ = 82

Low.average lo average Scaled Score

PIQ = 8.3

=7-12

A\erage Low-akerage .c s s 9

moderately Index = 76 : d e I3 y c d

5

Scaled Score = 8 - . h c r e l y lo Borderline t,

s Lou -average Aterage

381h sentile

Mildly dc layd to - low-aver3ge

patients ( I , 2 and 7) and bilateral in the other four. Visual acuity varied from normal vision in one eye to moderately reduced vision bilaterally (Table 11).

Neurological e.uaminarion Excluding the patients' ophthalmological examinations,--~urological findings indicated that all children had normal cranial nerve function. Muscle tone, bulk and strength were normal. When testable, sensory function was intact, including higher cortical sensations such as graphesthesia and finger gnosis. Deep tendon reflexes were normal and there was no evidence of pathological reflexes. No tremor or dysmetria was detected. One subject (patient 5 ) was tactilely defensive (unwilling to explore or touch objects). Three patients (3, 5 and 6 ) mani- fested delayed gross motor function to some degree: patient 3 was limited in her ability to stand on one foot and tandem walk; patient 5 was unable to climb stairs with alternating feet, run in a co-ordinated manner and consistently hop; and patient 6 had difficulty walking on his toes, jumping, climbing stairs and running.

Neuropsychological arid speech/language e.uarninarioris COGNITIVE FUNCTIONING The patients were all within the mildly delayed to superior range of intelligence (Table 11). The mean I Q score for the three oldest patients was within the high- average range (mean 115), while the younger children scored within the mildly delayed to low-average range. The youngest patient (7) had his 1Q estimated, due to oppositional behavior during testing: he scored in the average to high- average range on subtests measuring assembling familiar forms from memory (Object Assembly = 10) and visual plan- ning (Mazes = IZ), while his expressive vocabulary skills (Vocabulary = 7) were within the borderline to low-average range.

Of the six patients with complete measures of verbal and non-verbal intelligence, five demonstrated no significant difference between Verbal and Per- formance IQ scores. The Performance I Q of patient 1 was 19 points higher than her Verbal IQ. None of the patients demonstrated evidence of cognitive perseveration 493

i - _I

Y : < ACHIEVEMENT

except for patient 5 , whose IQ was within the mildly delayed range.

None of the school-age children had been 2 diagnosed as having learning disabilities 2 or had received special education services.

R appropriate achievement skills for her 0" measured abilities: her scores in reading - 2 (standard score' = loo), spelling (standard

score= 104), mathematics (standard score= 91) and reading comprehension (standard

vl score = 105) were within the average range. Although patient 2 was placed in 'gifted and talented' classes at school, his achievement skills during the present assessment were below expectations for his measured abilities. However, his performance was within the average range in reading (standard score = 94), spelling (standard score = 102) and mathematics (standard score = 108), and his errors in basic skills were related to impulsive responses. Patient 3 also demonstrated academic skills in reading (standard score = 85) and spelling (standard score = 98) below expectations for her cognitive abilities, while her mathematics score (108) ' was within the expected range. However, her performance was scored according to age-based norms, and she had not started the first grade. She could already read and spell single words, and results from standardized achievement tests indicated that her basic skills were within the high-average to superior range. Patient 4 demonstrated pre-academic skills (standard score = 93) and knowledge (standard score = 104) above expectations for her measured cognitive abilities. Patient 5 could not be assessed because of problems with visual acuity and cognitive delay. Measurement of pre-academic skills for patient 6 indicated that his pre- reading skills (standard score = 90) were developing beyond expectations for his abilities, while his pre-mathematics (standard score = 73) and pre-spelling skills (standard score= 69) were somewhat delayed. There was no significant discrepancy between his skills and measured cognitive abilities. Patient 7 refused to participate in any pre-academic tasks. Evaluation results suggested

494 no evidence of significant learning

.- 5L - 0

rs .- Lo The oldest patient (1) demonstrated -

n

- x C

disabilities for any of the patients assessed.

LANGUAGE All of the patients demonstrated language skills within or above expectations for their verbal intelligence (Table 11). Patient I had low-average receptive vocabulary skills (standard score = 89), while her confrontational naming skills' were within the average range. Her language skills were commensurate with her verbal intelligence, although there were indications of weaker verbal comprehension skills on both cognitive and language tests. Patients 2 and 3 had above-average language skills on the Clinical Evaluation of Language Fundamentals-Revised (standard scores= 121 and 125, re- spectively). Patierit 4 demonstrated low- average language skills on the Test for Auditory Comprehension of Language- Revised (TACL-R) (standard score = 87). However, she appeared to have skills within the average range on the Test of Language Development-Primary (TOLD-') (Spoken Language = 97, Listening = 87, Speaking = 105, Semantics = 94, Syntax = 94 and Phonology = 106). Her receptive vocabulary skills were within the average range (standard score= 104). Patient 5 displayed severely delayed receptive vocabulary skills (standard score = 66), while his expressive vocabulary skills were within the moderately delayed range (standard score = 71). The TOLD-2 was attempted, but he was unable to complete the tasks due to visual acuity and attentional difficulties. However, he was able to respond to the Grammatical Com- pletion subtest, and scored within the average range (scaled score = 9). He demonstrated perseveration when responding to questions during the language assessment, as well as during conver- sational speech. His overall language abilities were commensurate with his measured cognitive abilities. Patient 6 demonstrated low-average language skills on the TACL-R (standard score = 88). Patient 7 demonstrated an overall performance in the mildly delayed range

'Raw score transformed to a given mean and standard deviation. Word-finding skills or the ability to name an object when shown a picture or representation of it.

TABLE 111 Non-verbal skills

~

I l9:2

2 I 2 4

3 6:9

4 1:s

5 J:B

6 3:9

7 3 : l

Superior 99th cenlile

Low-average 16th centile

High-average PQ'= I I ?

Low-average PQ = RS

Borderline Staled Score = 7

Average Scaled Score = 9

NA

Superior Index = 124

Average Index= 105

Average Index = 96

Low-a\ erage Scaled Score

NA

Low-avcrage

N A '1st ccntile

~

Superior

Average

Averagc

Aberage = 8 Scaled Scorc = 107

Borderline

Avcrage

Average

99th centile

Scalcd Scorc = 107

Scaled Scorc = 99

Scaled Score = 79

Scaled Score = 93

Scaled Scor.: = 93

~-

Intact

Intact

Poor co-ordination

Adequate

hloderaiely I O N

Xloderately l ow

Adequte

Standard Score = 93

Standard Score = 51

Standard Score = 56

Standard Scorc = SS

'PQ = Perceptua l Quot ienr.

on the TACL-R (standard score = 75). However, there was significant scatter among his skills (Word Classes = 74, Grammatical Morphemes = 89 and Elabor- ated Sentences = 96). His expressive vocabulary skills were within the low- average range (standard score = 88), while his receptive vocabulary skills were within the mildy delayed to low-average range (standard score = 79).

The two patients (5 and 7), who were administered the Goldman Fristoe Test of Articulation, had articulation skills within the normal range. There were no speech production errors noted for any of the other patients.

VERBAL MEMORY Verbal memory skills were within or above expectations for measured cognitive abilities in five of the patients (Table 11). Patient 1 was able to learn a word-list, her

. recall of digits and word-pairs was within the average range, and she showed no decrement in verbal memory over time. Her scores were lowered by difficulty with recall of story paragraphs, resulting from weaker verbal comprehension skills rather than from retrieval or encoding problems. Patient 7 refused to co-operate on memory tasks.

VISUAL-SPATIAL SKILLS Visual-spatial skills were within or above expectations for measured cognitive abilities in five of the seven patients

(Table I l l ) . Patient 2 tended to respond in a highly impulsive manner which lowered his performance, while patient 7 was unco-operative with the measurement of these skills.

VISUAL MEMORY Significant discrepancies were noted between the verbal and visual memory skills of three patients (Table HI). Patient 1 demonstrated superior visual memory skills, which were significantly more developed than her verbal memory skills. Patients 2 and 3 displayed significantly stronger verbal than visual memory skills, although their visual memory skills were within the average range. Patient 4 demonstrated low-average visual memory skills which were within expectations for her measured abilities. Visual memory could not be assessed in patient 5 because of visual acuity difficulties. Patient 6 had low-average visual memory skills, commensurate with his cognitive functioning. Patient 7 refused to complete the visual memory tasks.

VISUAL-MOTOR INTEGRATION Visual-motor integration was within or above the average range for six of the children (Table 111). Patient 1 demonstrated superior skills on her completion of a complex figure drawing. Only patient 5 had some delay in visuo-constructional skills: his performance was within the borderline range. Modifications, which 495

i h aI -. consisted of allowing the child to draw the

shapes outside the designated area, had to be made for patient 5 because of visual difficulties and for patient 7 because of refusal to co-operate during the task.

GROSS MOTOR SKILLS Developmental reports indicated that four of the patients had reached motor milestones within normal limits, as measured by walking and riding a tricycle. However, there was some reported motor clumsiness for all of the patients. Patient 4 did not start to walk until 18 months of age. Patient 5 was significantly delayed in both walking and riding a tricycle, and did not walk until two years of age. Patient 6 still could not ride a tricycle at nearly four years of age.

Present assessment indicated that four patients had adequate gross motor skills (Table 111). Patient 1 played basketball in school, and patient 2 played football and volleyball. Patient 3 had problems with inco-ordination, as was noted on the neurological evaluation. Patient 4’s motor skills were within the normal range. Patient 5 had significant motor delay: he needed assistance in walking downstairs with alternating feet, he could not hop forward continuously even while holding onto another person, and his running was generally inco-ordinated. He demonstrated tactile defensiveness during the evaluation, and flapped his hands when he became excited. Patient 6 also had significant motor delay: he ran in an inco-ordinated manner, he could not consistently jump over a small object, and he could not hop forward continuously while holding onto another person. Patient 7 displayed motor skills in the normal range, although he could not hop forward with support or walk downstairs with alternating feet.

PSYCHOMOTOR SKlLLS Four of the patients (1, 2 3 and 5 ) were right-handed for pencil and paper tasks. Two patients (4 and 6 ) were left-handed for writing tasks, although patient 6 was inconsistent. Patient 7 had not established hand dominance.

Pure motor speed was measured by the Finger-tapping Test for the three oldest

496 patients: patient 1 demonstrated low-

average to average speeds bilaterally, with the expected dominant-hand advantage noted; patient 2 demonstrated low- average speeds bilaterally, with a slightly greater than expected dominant-hand advantage; and patient 3 demonstrated superior bilateral speeds, with a greater than expected dominant-hand advantage.

On the Grip-strength Test, patient 1 demonstrated borderline to low-average strength, with a slightly greater than expected dominant-hand advantage; patient 2 had very superior grip-strength bilaterally, with a slightly less than expected dominant-hand advantage; and patient 3 demonstrated borderline strength bilaterally.

Speed of visual-motor integration on the Grooved Pegboard Test indicated that patient 1 had average scores for her dominant hand, while performance of her non-dominant hand was within the low- average range; she had a significantly greater than expected dominant-hand advantage. Patient 2 demonstrated superior speed for his dominant hand, while his non-dominant hand was within the borderline range; a significantly greater than expected dominant-hand advantage was noted on this task. Patient 3 displayed speed within the average range for her dominant hand, but within the low-average range for her non-dominant hand; there was a significantly greater than expected dominant-hand advantage. Patient 4, who was left-handed, demonstrated average speeds bilaterally with no difference bet ween hands.

SENSORY-PERCEPTUAL FUNCTIONING Intact perception was demonstrated for those patients (1 and 2) given simple tests of auditory, tactile and visual stimulation, except for some items that relied on peripheral vision. Intact-form recognition was displayed by children administered these tasks (patients 3 and 4). Tactile integration was intact for two of three subjects (patients 1 and 3) for finger-tip writing items, but the third (patient 2) made a slightly greater than expected number of errors: his performance was felt to be affected by his impulsive response style. Finger localization was intact for those administered these tasks (patients 1 and 3).

TABLE IV Adaptiw brhs,iourlpersonalil?

hlblPI Nor nia I proftlc

CBCL Nurnial Normal range H y r a c t i w Norrnal range KormaI range Normal rance t > r311gc T =iO'

Sosialirarion

DmI! l iving Allk

5 9 P

'h.lMP1 =Minnesota Multiphasic Penonality Inventory; CBCL = Child Behavior Checklist; CPRS = Conners Parent Raiirig Scale; VABS = Vineland Adaptive Behavior Scalcs. 'SS = ar3ndard score. 'T=T (core (a standard worc with mean SO, S D ? 101. clinic all^ cleLared

Two patients ( 3 and 4) were given the Right-left Confusion subtest of the McCarthp Scales of Children's Abilities: they performed within the average to high- average range in discriminating directional positions, according to age-based norms.

EXECUTIVE FUNCTIONING Cognitive llesibility was within the normal range for the three patients tested ( I , 2 and 3 ) ; none had a significant number of perseverative errors. However, patients I and 3 had a greater number of failures to maintain set* than would be expected based on age norms. Psychomotor speed and visual sequencing were within the high-average range for those administered the Trail Making Test Part A (patients I and 2). For Part B, patient 1 scored within the low-average range with no errors, while patient 2 scored within the average to high-average range with one impulsive error. Test results indicated intact problem-solving skills for the three oldest patients, with some quantitative suggestions of inat tent ion.

On tests of attention and concentration, patient 1 was given the Attention- Concentration Scale of the Wechsler

*A loss of problem-solving strategy: [he child does not maintain the same strategy and iails to solve the problem set.

4

Memory Scale-Revised. She performed within the average range (Index = iO2); however. she made two errors when reciting the alphabet. Patients 2 and 3 were given a computerized test of visual attention. Patient 2 displayed generally intact attention, but had problems with impulsiveness when responding. His score (scaled score=6) on a separate test of visual sequencing indicated inattentive- ness to visual details. He also demonstrated a relative weakness on the Freedom From Distractability factor of the WISC-R, compared with his conceptual skills. Patient 3 had significantly delayed visual attentional skills on the computerized test of atten tion.

ADAPTIVE BEHAVIOR AND PERSONALITY Patient 1 was given the Minnesota Multiphasic Personality Inventory to assess emotional functioning. The clinical scales were all within the normal range, with some suggestion of social conformity and shyness. Parental perceptions of the remaining patients on the Child Behavior Checklist indicated behavioral functioning within the normal range except for patient 4, whose profile indicated an elevation on the Hyperactive Scale: her mot her per- ceived her as being impulsive and hyperactive, as well as having difficulty in 49 7

J ;

498

concentrating. On the Conners Parent Rating Scale, four of six children had normal profiles. Significant elevations were noted for two patients (4 and 6) on the Psychosomatic Scale, as a result of these children's frequent headaches of unknown etiology. The Conners Teacher Rating Scales were within normal limits for the two school-aged children (patients 2 and 3).

Adaptive behavior was within the adequate range for four of five children: these four demonstrated normal development in the areas of communication, socialization and daily living skills, while the fifth (patient 5 ) had delayed development of adaptive skills.

Behavioral observations during the neuropsychological and speechAanguage evaluations indicated good attentional skills for patient 6. Patients 1 and 3 were visually inattentive. Patient 2 was impulsive in his response style, and would answer questions before they were completed. Patients 4 and 5 had short attention spans, and they demonstrated difficulty scanning and attending to visually presented materials. Patient 7 had adequate attentional skills for high- interest tasks, but was unco-operative and distractible for all other items.

Discussion Six of seven children with optic nerve hypoplasia and absence of the septum pellucidurn demonstrated cognitive development within the normal range, with no diagnosed learning disabilities. These six patients showed no significant discrepancy between verbal and non- verbal skills except for one, who demonstrated stronger non-verbal abilities. Language and verbal memory skills were intact, and the language skills of two children were above the normal range. Of the seven patients, only one demonstrated moderate cognitive and language delays: this patient had the poorest visual acuity of the group, and the examiners felt that his inability to scan test items decreased his performance, although his visual impairment did not fully explain his developmental delays. More significantly, a re-examination of his MR scan disclosed mild periventricular leukomalacia.

Contrary to experimental results in

'

animals, the patients showed no spatial- cognition deficits: visual-spatial skills were generally within the normal range; visuo-constructional skills were intact for six of the patients when modifications of visual materials were made; and although two patients demonstrated significantly stronger verbal than visual memory skills, there were no indications of deficits in visual memory.

The extent to which visual impairment interferes with the acquisition of normal developmental milestones in young children is not clear. Previous studies have demonstrated that fine and gross motor development tend to be delayed for infants and preschool children with severe visual impairment or blindness (Bradley- Johnson 1986). In the present study, motor development was within the normal range for four of the seven patients, although there were consistent reports of earlier clumsiness and 'incoordination for all subjects. Three patients had unilateral optic nerve hypoplasia, permitting a more objective assessment of motor skills. In these three, who had, normal test results, early motor skills were only minimally affected. Most of the children in our study had mild to moderate visual deficits, thereby mini- mizing the confounding effects of visual impairment on their ability to perform. However, the trend toward improved motor skills and cognition with age in our sample suggests that visual skills do play an influential role in early development.

Adaptive behavior for all patients with normal cognitive development was within the normal range. Although parent rating scales generally did not reflect clinical hyperactivity, there were consistent signs of subtle attention deficits during the testing of all children except one: the inattention was confined primarily to visual details and sequencing tasks. For some of the children, visual scanning was limited. Although the finding of inattention is consistent with experimental evidence indicating abnormal behavioral inhibition in animals following lesions to the septum pellucidurn, i t is possible that even mild degrees of visual impairment may have contributed to the subtle attention deficits seen in our patients.

We conclude that absence of the septum

pellucidum alone does not portend significant intellectual, neurological or behavioral dysfunction. Our results suggest that the findings of cerebral palsy, epilepsy, mental retardation and behavioral disturbance in previous studies of patients with optic nerve hypoplasia do not result from absence of the septum pellucidurn alone and probably reflect co- existent cerebral hemispheric abnormalities. Additional analyses of children with specific anomalies based on hlRl are needed. Results of this study imply a favorable neurodevelopmental prognosis for children with septo-optic dysplasia after cerebral hemispheric and infundibular abnormalities have been carefully excluded. Accepted .tor publication 25th Novembsr 1992.

A ckno dedgements Special appreciation is expressed to Nettie Koshoffer for technical assistance. This project was supported in part by a grant from Research to Prevent Blindness, Inc.

A irthors ’ Appoinlments ‘Jane Williams, Ph.D., Department of Pediatrics; Michael C . Brodsky, M.D., Department of Ophthalmology: May Griebel, h.1.D.. Department of Neurology: Charles M. tilasier, M.D ... Department of Radiology; University of Arkansas for Medical Sciences. Diana Caldwell. M.S., C.C.C.. S.L.P.; Phyllis Thomas, hl.A..; Arkansas Children’s Hospital, Dennis Develop- mental Center.

‘Correspondence to first author at University of Arkansas for Medical Sciences, Department of Pediatrics, 800 Marshall Street, Little Rock, AR 72202.

SUMMARY Neurodevelopmental assessments were performed on seven patients with optic nerve hypoplasia and absence of the septum pellucidum on MRI. The evaluation included neurological status, language development, neuropsychological functioning, and behavioral and emotional adjustment. Six of the seven were found to have normal cognitive development, intact neurological status, normal language development and age-appropriate behavior. Abnormal findings included early poor motor co- ordination, which was felt to be closely related to decreased visual acuity, as well as subtle visual attentional problems which occurred even in patients who had normal vision in one eye. Congenital absence of the septum pellucidum was not associated with significant intellectual, behavioral or neurological deficits in the majority of these patients.

RESUME Dysplasie septo-oprique: signification clinique d ’un sepruni lucidurn manquant Une evaluation neurodeveloppementale a i t e realisee chez sept patients prksentant une hypoplasie de nerf optique et une absence du septum lucidum B I’IRM. L’evaluation incluait un examen neurologique, le niveau de developpement du langage, le fonctionnement neuropsychologique et I’integration comporternentale et emotionnelle. Chez six des sept patients, il fut note un developpement cognitif normal, un examen neurologique normal, un developpement du langage normal et un comportement approprie a I’ige. Les donnees anormales incluaient une incoordination motrice precoce qui semblait etroitement reliee a la diminution de I’acuite visuelle, ainsi que des problemes minimes d’attention visuelle survenant mOme chez les patients ayant une vision normale d’uri oeil. L’absence congenitale du septum lucidum n’etait associee B aucun deficit intellectuel, comportemental ou neurologique significatif chez la majorite de ces patients.

ZUSAMMENFASSUNG Seprutn-Oplicus D-vsplusie: Klinische Bedeurung eines fehlenden Septum pellucidum Bei sieben Patienten, bei denen im MRI eine Hypoplasie des N.opticus und ein Fehlen des Septum pellucidum nachgewiesen worden war, wurden entwicklungsneurologische Untersuchungen durchgefuhrt. Es wurden neurologischer Status, Sprachentwicklung, neuropsychologisches Verhalten und allgemeine und emotionale Anpassung beurteilt. Sechs der sieben Patienten hatten eine normale kognitive Entwicklung, einen unauffalligen neurologischen Status, eine normale Sprachentwicklung und ein altersentsprechendes Verhalten. Die pathologischen Befunde bestanden in frijhen motorischen Koordinationsstorungen, die wahrscheinlich durch verminderte Sehscharfe, sowie leichte Probleme bei der visuellen Aufrnerksarnkeit bedingt waren, sie traten sogar bei Patienten auf, die auf einem Auge ein normales Sehvermogen hatten. Das kongenitale Fehlen des Septum pellucidum war bei der Mehrzahl de Patienten nicht mit intellektuellen, das Verhalten betreffenden oder neurologischen Storungen verbunden.

RESUMEN Dispiasia septo-optica: significado clinic0 de un septum pelucidum ausente Se practico una evaluacion neuroevolutiva en siete pacientes con hipoplasia del nervio 6ptico y ausencia del septum pelucidum comprobada por IRM. La evaluacibn incluy6 el estatus neurolbgico, el desarollo del lenguaje, las funciones neuropsicol6gicas y la adaptaci6n conductal y emotiva. Se ha116 que seis de 10s siete casos tenian un desarrollo cognitivo normal, un estatus neurolbgico

- s: 0 a 7

‘A M

Y - 4 B

499

v c

.- - 0 i

500

intacto, un normal desarrollo del lenguaje y una conducta apropiada por ia edad. Los hallazgos anormales consistian en una incoordinacion motora precoz, que se ha116 que estaba intimamente relacionada con la disminucion d e la agudeza visual, asi c o m o problemas sutiles d e atencion visual que se daban incluso en nirlos con vision normal d e un ojo. La ausencia congenita del septum n o iba asociada a deficits significativos intelectuales, conductales o neurologicos en la mayoria d e estos pacientes.

References Acers, 1. E. (1981) ’Optic nerve hypoplasia: septo-

optic-pituitary dysplasia syndrome.’ Transactions of ihe American Ophthalmological Society, 79,

Barkovich, A. J . . Fram. E . K., Norman, D. (t989) ‘Sepro-optic dysplasia: MR imaging.’ Radiology,

Bradley-Johnson, S. (1986) Psychoeducational Assessment of Visually Impaired and Blind Students: In fancy through High School. Austin. TX: Pro-Ed.

Brodsky, M. C. (1991) ‘Septo-optic dysplasia: a reappraisal.’ Seminars in Opiuhalmology, 6,

- Glasier, C . M.. Pollock, S. C., Angtuago, E. J . C. (1990) ‘Optic nerve hypoplasia: identi- fication by magnetic resonance imaging.’ Archives of Ophthalmology, 108, 562-567.

de hlorsier, G . (1956) ‘Etudes sur les dysraphies cranio-encephaliques. 111: AgenCsie du septum lucidum avec malformation du tractus optique: la dysplasie septo-optique.’ Schweizer Archiv f i r Neurologie und Psychiatrie, 12, 261-292.

Douglas, R. J . , Raphelson, A. C. (1966) ‘Spon- taneous alternation and septa1 lesions.’ Journal o/ Comparafive and Physiological Psychology, 62, 320-322.

Fielder, A. R., Mayer. D. L. (1991) ‘Delayed visual maturation.’ Seminars in Ophthalmology, 6,

Fried, P . A. (1972) ‘Septum and behaviour: a review.’ Psychological Bulletin, 78, 292-3 10.

Griffiths, P., Hunt, S. (1984) ‘Specific spatial defect in a child with septo-optic dysplasia.’ Develop- mental iZ Iedicine and Child Nc’urofog.v, 26. 395400.

Hoyt, W. F. Kaplan, S. L., Grumback, M. M., Glaser, J . (1970). ‘Septo-optic dysplasia and pituitary dwarfism. Lancet, 1, 893-894.

Kaufman, L. M., Miller, M. T., MaFee, M. F. (1989) ‘Magnetic resonance imaging of pituitary stalk hypoplasia: a discrete midline anomaly associated with endocrine abnormalities in septo- optic dysplasia.’ Archives of Ophfhalmology,

Kelly, W. M., Kucharczyk, W., Kurcharczyk, J., Kjos, B., Peck, W. W., Norman, D., Newton, T. H. (1988) ‘Posterior pituitary ectopia: an MR feature of pituitary dwarfism.’ American Journal of Neuroradiology, 9, 453-460.

Margalith, D., Jan, J . E., McCormick, A. Q., Tze, W. J . . Lapointe, J . (1984) ‘Clinical spectrum of congenital optic nerve hypoplasia: review of 5 1 patients.’ Developmental Medicine and Child Neurology, 26, 31 1-322.

Sarwar, M. (1989) ‘The septum pellucidum: normal and abnormal.’ American Journal of Neuro- radiology, 10, 989- 1005.

Skarf, B., Hoyt, C. S. (1984) ‘Optic nerve hypoplasia in children: association with anomalies of the endocrine and CNS.’ Archives of Ophthalm-

Smhl, J. M., Ellen, P. (1973) ‘Septal lesions and reasoning performance in the rat.’ Journal of Comparafive and Ph-vsiological Psychology, 84, 629-638.

425-451.

171, 189-192.

227-232.

182- 193.

107, 1485-1489.

ology, 102, 62-61.

References to iesis irsed Achenbach, T. M. (1991) Child Beita~ior Checklisr for Ages 4-18. Burlington. VT: University of Vermont Department of Psychiatry.

Beery, K. E. (1989) Developntental Tesi of Visual- Motor Intcyrarion. 3rd Edn. Cleveland. OH: Modern Curriculum Press.

Benton, A. L., Hamsher, K., Varney, N. R., Spreen, 0. ( 1 9 8 3 ~ ) Judgmenr of Line Orienfation Test. New York: Oxford University Press.

- - - _ (19836) Visual Form Discrimin- aiion Test. New York: Oxford University Press.

Carrow-Woolfolk, E. (1985) Test for Auditory Comprehension of Language. Allen, TX: DLM Teaching Resources.

Colarusso, R. P., Hammill. D. D. (1971) Motor- Free Visual Perception Test. Novato, CA: Academic Therapy Publications.

Conners, C. K. (1982) ‘Parent and teacher rating forms for ihe assessment of hyperkinesis in children.’ In Keller, P . A, . Ritt. L. G. (Eds.) Innovations in Clinical Practice. Vol. I . A Resource Book. Sarasota. FL: Professional Resource Exchange.

Dunr.. L. M., Dunn, L. M. (1981) Peabody Picture Vocabulary Test-Retised, Form L . Circle Pines. MN: American Guidance Service.

Gardner, M . F. (1990) Expressive One- Word Picture Vocabulary Test-Revised. Novato, CA: Academic Therapy Publications.

Goldman, R., Fristoe, M . (1986) Goldman-Frtsroe Tesf of Articulation. Circle Pines. MN: American Guidance Service.

Hathaway, S. R., McKinley, J . C. (1985) Afinnesofu hfuliiphusic Personaliry f n venfor.v. Mi n nea pol ic . MN: National Cornpurer Sysiems, Inc.

Heaton, R. K. (1981) Wisconsin Curd Sorling Tea. Odessa, FL: Psychological Assessment Resources.

Jastak. S., Wilkinson, G . S . (1984) Wide Range Achievement Tesf-Revised. Wilmington, DE: Jastak Associates.

Kaplan, E., Goodglass, H. , Weintraub, S. (1982) Boston Naming Test: Revised Edition. Boston, MA: Boston University.

Klove, H. (1963) ‘Clinical neuropsychology.’ Medical Clinics of North America, 47,

Loons, J . W. K. (1988) Continuous Performance Test. Sari Luis Obispo, CA: Wang Neuro- psychological Laboratory.

McCarthy, D. (1972) McCarthy Scales of Children’s Abilities. New York: Psychological Corporation.

Newcomer, P. L., Hammill, D. D. (1988) Test of Language Development- Primary. Aust in, TX : Pro-Ed.

Osterrieth. P. A. (1944) ‘Le test de copie d’une figure complexe.’ Archives de Psychologie, 30, 206-356.

Reitan, R. M., Davison, L. A. (1974) Clinical Neuropsychology: Currenf Status and Appli- cations. Washington, DC: V. H . Winston.

Rey, .4. (1964) L ‘Esameti Cliniyue en Psvchologie. Paris: Presses Universitaires de France.

Semel, E., Wiig, E . H., Secord, W. (1980) Clinica: Evuluarion of Language Fundamenfals-Revised. New York: Psychological Corporation.

1647- 1658.

Sheslow, D., Adams, W. (1990) Wide Range Revised. New York: Psychological Corporation. Assessnienr o j Mernor.v and Learning. - (1987) Wechsler Xletnor.v Scale-Revised. New Wilmingron, DE: Jastak Associates.

Sparrow, S. S., Balla. D. A., Cicchetti, D. V. (1984) - (1989) Weclrsler Preschooi and Primary Scale Vineland Adapritfe bleharior Scales. Circle Pines, of Inlelligence-Revised. New York: Psycho- MN: American Guidance Service.

Wcchsler, D. (1974) Wechsler Inielligence Scalejor Woodcock, R. W . , Johnson, M. B. (1977) Children-Revised. New York: Psychological Woodcock-Johnson Psycho-Edticational Barter!. Corporation.

- (1951) W'echsler Adirlr Inrc.lligenc-e Scale-

York: The Psychological Corporation.

logical Corporation.

Allen, TX: DLM Teaching Resources.

501

SEPTO-OPTIC DYSPLASIA: THE CLINICAL INSIGNIFICANCE OF AN ABSENT SEPTUM PELLUCIDUM

Documents

Transcript of SEPTO-OPTIC DYSPLASIA: THE CLINICAL INSIGNIFICANCE OF AN ABSENT SEPTUM PELLUCIDUM