eeg recognition of holoprosencephaly and aicardi syndrome

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Indian J Pediatr 1992; 59 : 103-108 II EEG Recognition of Holoprosencephaly and Aicardi Syndrome K.N. Shah, Surekha Rajadhyaksha, V.S. Shah and M. Wakde Department of Pediatrics, Medicine, Bai Jerbai Wadia Hospital for Children & Institute of Cluld Health, Acharya Donde Road, Parel, Bombay Two cases of alobar holoprosencephaly and two of Aicardi syndrome are reported for their highly specific electroencephalographic (EEG) changes. The asynchronous sharp waves and spikes over the frontal regions with de- creasing gradient of potential to the occipital leads were seen in alobar hol- oprosencephaly while burst suppression pattern with total asynchrony be- tween the two hemispheres was seen in Aicardi syndrome. Even though EEG changes cannot be pathognomic of any abnormality, it is suggested that as in conditions like subacute sclerosing panencephalitis and petitmal epilepsy, so also in alobar holoprosencephaly and Aicardi syndrome, the characteristic features seen on EEG may provide the initial clue to the correct diagnosis. Key ~'r EEG; Holoprosencephaly; Aicardisyndrome. Holoprosencephaly is a rare malformation of the forebrain with an estimated fre- quency of 1:13,000 births I where there is a marked disturbance in the development of both telencephalon and diencephalon, and results in the formation of a single Sphered cerebral structure with a common ventricle and may be associated with severe facial anomalies. Aicardi syndrome is character- ised by association of multiple congenital anomalies, in a female child with infantile spasms, mental retardation, agenesis of cor- pus callosum with distinctive chorioretinal lacunae and osseous anomalies. We report our experience of two cases of alobar ho- moprosencephaly and two of Aicardi syn- Reprint requests : Dr. K.N. Shah, Professor of Pediatrics, B.J. Wadia Hospital for Children & Institute of Child Health, Parel, Bombay 400012. drome wherein the highly specific EEG changes formed an important tool in the diagnosis of these conditions. Case 1. A two day old female child born of first degree consanguinous marriage, was admitted in the neonatal ward with history of high fever for one day and repeated con- vulsions since birth. The convulsions ob- served were in the form of myoclonic jerks. Both the pregnancy and delivery were un- eventful. Patient was the first child in the family without any family history of similar illness. On examination the baby weighed 2.1 kg with head circumference of 30.5 cm, length of 48 era and was tachypneic with respira- tory rate of 72/rain. There was ceboccphaly i.e. ocular hypotelorism with a flat single nose, microcephaly with small anterior fon- taneUe, palpable metopic suture, cleft lip 103

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Indian J Pediatr 1992; 59 : 103-108 II

EEG Recognition of Holoprosencephaly and Aicardi Syndrome

K.N. Shah, Surekha Rajadhyaksha, V.S. Shah and M. Wakde

Department of Pediatrics, Medicine, Bai Jerbai Wadia Hospital for Children & Institute of Cluld Health, Acharya Donde Road, Parel, Bombay

Two cases of alobar holoprosencephaly and two of Aicardi syndrome are reported for their highly specific electroencephalographic (EEG) changes. The asynchronous sharp waves and spikes over the frontal regions with de- creasing gradient of potential to the occipital leads were seen in alobar hol- oprosencephaly while burst suppression pattern with total asynchrony be- tween the two hemispheres was seen in Aicardi syndrome. Even though EEG changes cannot be pathognomic of any abnormality, it is suggested that as in conditions like subacute sclerosing panencephalitis and petitmal epilepsy, so also in alobar holoprosencephaly and Aicardi syndrome, the characteristic features seen on EEG may provide the initial clue to the correct diagnosis.

Key ~'r EEG; Holoprosencephaly; Aicardi syndrome.

Holoprosencephaly is a rare malformation of the forebrain with an estimated fre- quency of 1:13,000 births I where there is a marked disturbance in the development of both telencephalon and diencephalon, and results in the formation of a single Sphered cerebral structure with a common ventricle and may be associated with severe facial anomalies. Aicardi syndrome is character- ised by association of multiple congenital anomalies, in a female child with infantile spasms, mental retardation, agenesis of cor- pus callosum with distinctive chorioretinal lacunae and osseous anomalies. We report our experience of two cases of alobar ho- moprosencephaly and two of Aicardi syn-

Reprint requests : Dr. K.N. Shah, Professor of Pediatrics, B.J. Wadia Hospital for Children & Institute of Child Health, Parel, Bombay 400012.

drome wherein the highly specific EEG changes formed an important tool in the diagnosis of these conditions.

Case 1. A two day old female child born of first degree consanguinous marriage, was admitted in the neonatal ward with history of high fever for one day and repeated con- vulsions since birth. The convulsions ob- served were in the form of myoclonic jerks. Both the pregnancy and delivery were un- eventful. Patient was the first child in the family without any family history of similar illness.

On examination the baby weighed 2.1 kg with head circumference of 30.5 cm, length of 48 era and was tachypneic with respira- tory rate of 72/rain. There was ceboccphaly i.e. ocular hypotelorism with a flat single nose, microcephaly with small anterior fon- taneUe, palpable metopic suture, cleft lip

103

104 TIlE INDIAN JOURNAL OF PEDIATRICS Vol. 59, No. 1

and p*,date, low set cars with absent antihe- lix and wide set nipples. There were no de- formities of the fingers and toes suggestive of any chromosomal anomaly. Systemic ex- amination did not reveal any abnormal find- ings. On the basis of these clinical findings a diagnosis of holoprosencephaly was made.

Routine investigations like blood count, urine, serum calcium, electrolytes, blood sugar and cerebrospinal fluid were norm',d. EEG showed sharp waves, spi~e and wave, polyspike and wave complexes over frontal regions, more often asynchronous, more frequently and of higher amplitude over left frontal region throughout the record with decreasing gradient of potentials from the frontal to the occipital leads (Figure 1). Centrotemporal re#on showed high ampli- tude rh)'thmic delta activity at 1 cps with low amplitude to almost isoelectric record posteriorly (Figure 2). Ultrasonography of the head showed a single dilated ventricle and fused thalami. CT scan of the head showed gross evidence of abnormal organo- genesis in the form of a very large monol- ocular ventricle which was occupying most of the supratentorial compartment. No dif- ferentiation of the third or lateral ventricle was possible. The cerebral parenchyma was pushed towards the skull vault and seen in

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Fig. 2. Elcclroencephulogram (see text).

the form of a thick strip of brain tissue in frontal or frontoparietal areas. Identifica- tion of various lobes of the cerebrum was not possible and there was no evidence of sylvian fissure on either side. The thalami were fused together and visible as an abnor- mal rounded brain substance in the centre. The C-l" scan findings were consistent with alobar holoprosencephaly (Figure 3). Chro- mosomal studies were done to exclude trisomies as a possible cause of hol- oproscnccphaly, but unfortunately the yield

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Fig. I. Electroencephalogram (see text).

Fig. 3. C~I" scan of head showing monolocular ventricle and thick strip of brain tissue in frontal and frontoparietal areas.

SI IAH ET AL : EEG RECOGNI'I 'ION OF I IOLOPROSENCEPHALY 105

was inadequate to give any conclusive re- port and patient died before it could be re- peated.

Case 2. This four and a half month old male infant was referred for EEG, with a history of myoclonic jerks. No further information was given in the EEG request form about the clinical features of the infant. EEG showed frequent, asynchronous sharp waves, spikes, spike and wave and polyspike and wave complexes over both frontal re- gions with decreasing gradient of potentials over the frontal to occipital leads. It also showed as)anmetry over ce.ntrotcmporal

Fig. 4. Clinical photograph of Case 2 showing hypotelorism, depressed nasal bridge, single nostril and midline cleft lip.

region between right and left side with al- most isoelectric record posteriorly. As this record resembled the record of the previous case, the child was examined and investi- gated in detail. This infant was born of non- consanguinous parents by cesarean section for nonprogression of labour and meco- nium stained liquor, cried immediately after birth and had a normal Apgar score. Patient was the first child in the family without any similar illness in the relatives. Tonic spasms were observed during the first week of the life followed by frequent myoclonic jerks with which the baby was brought to us. On examination, baby weighed 5 kg with head circumference of 35 cm, length of 60 em and anterior fontanelle was just a dimple without any sutural overlap. There was proptosis, single nostril, midline cleft lip, partial deft palate, hypotelorism with bilat- eral coloboma of iris (Figure 4). No other abnormality was found in general as well as on systemic examination, uitrasonography of head revealed hydrocephalus. C~I" scan revealed a large CSF attenuation area with a thin rim of brain tissue in frontal and pa- rietal regions, The third ventricle was not identified separately and appeared to be part of the single lateral ventricle. The sep- turn peilucidum and inter-hemispheric fis- sures were not seen. Both thalami were fused. CT findings were indicative of alobar holoprosencephaly. Chromosomal study did not reveal any trisomy.

Case 3. A three month old female child born of a first degree consanguinous mar- riage was brought with a history of repeated episodes of convulsions observed were brief jerky movements involving the limbs with staring spells, later developed gencralised flexor spasms with a frequency of 5-10 per day. Both the pregnancy and delivery were uneventful. An older 3 year old daughter

106 T I I E I N D I A N J O U R N A L O F P E D I A T R I C S Vol. 59, No. 1

was normal and there was no family history of similar illness. Developmentally the in- fant had not achieved any milestones at 3 months of age.

On examination the baby's head circum- ferences was 37.5 cm, length 58 cm, she had occipital flattening and bilateral mi- cropthalmia. Systemic examination was nor- mal. She had brisk tendon jerks with clonus bilaterally. Fundus examination of right eye showed atrophic chorioretinitis and colo- boma of disc, while left eye revealed atro- phic chorioretinitis and glial proliferation. Routine blood, urine, serum calcium, cere- brospinal fluid were normal. Her VDRL and Toxoplasma antibodies both lgG and IgM were negative. Skeletal survey was nor- mal. Her EEG showed independent, asyn- chronous burst of medium voltage followed by suppression on left and right side sepa- rately (Figure 5).

Computerized tomogralphy (CT) showed evidence of abnormal organogenesis in the form of mildly dilated third ventricle which extended upwards to lie between the two bodies of lateral ventricle. The anterior interhemispheric fissure was abnormally deep reaching anterior part of third ven- tricle. Lateral ventricles were separated from each other and showed parallel

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Fig. 5. Electroencephalogram (see text).

configuration. CT scan findings were highly suggestive of dysgenesis of corpus callosum (Figure 6).

Case 4. This was a 7 month old female child born of a non-consanguinous marriage, af- ter a full term uneventful delivery, who pre- sented with generalised tonic clonic convul- sions two days after her 1st triple immuni- zation at 3�89 months of age. Subsequently she developed repeated myoclomc jerks, 4-5 episodes occurring in one day. The baby had gross psychomotor retardation with non-achievement of any milestones.

On examination she had no dysmorphic facies, her head circumference was 40 cm, length 63 cms, weight 7 kg with no skeletal anomalies. Her systemic examination was normal. Her ophthalmic examination re- vealed bilateral coloboma with macular and choroidal degeneration. Her EEG was grossly abnormal with multifocal neuronal hyperexcitability with burst suppression pat- tern occurring independently and asynehro- nously in the two hemispheres suggestive of Aicardi syndrome. Her CT scan conf'u'med the highly placed third ventricle with break- ing of frontal horns suggestive of dye, genesis of corpus callosum. She was treated with sodium valproate 30 mg/kg in 4 divided doses with good control of her myoclonic seizures.

DISCUSSION

DeMyer and White 2 described very charac- teristic EEG pattern in five infants with everted frontal alobar holoprosencephaly which include decreasing gradient of poten- tials from the frontotemporal leads located directly over the holoprosencephalon to the occipital leads over the dorsal sac, several centimeters away from the electrically active tissue and an intermixture of

SHAll El" AL : EEG RECOGNITION OF ! IOI.OPROSENCEP| IAI.Y 107

Fig. 6. CT scan showing abnormal organogene- sis in form of mildly dilated third ven- tricle extending between the two bodies of lateral ventricle.

asynchronous spikes, sharp waves and slow waves, periodic complexes, and hypcrsyn- chronous bursts terminating into high am- plitude, rhythmic activity of 1 cps which be- came generalised. Both our cases showed alobar holoprosencephaly on CT scan of head and had characteristic EEG changes as described above. Although isoelectric or almost flat changes are described in cere- bral destructive lesions like hydrancnceph- aly and porencephaly, fluid accumulation such as haematomas, hygromas, a combina- tion of inactivity posteriorly and bizarre ac- tivity anteriorly is not seen in any other con- dition except everted alobar hol- oprosencephaly.

Aicardi syndrome with multiple congeni- tal anomalies, agenesis of corpus callosum associated ~ t h infantile spasms is charac- teristically described in females or those with 47,XXY karyotype. The existence of a X-linked locus for this disease has been suggested. 3 The unicity of EEG findings and

the independent activity over the two hemi- spheres was emphasiscd by Dennis and Bower and confirmed the opinion shared by others who felt that EEG may provide the first clue in the diagnosis. 4 Fariello et al re- viewed the EEG findings and stated that the background activity in Aicardi syn- drome reveals a burst suppression pattern with a total asynchrony between the two hemispheres as though arising from differ- ent brains. The asynchrony was more evi- dent in the early course of illness within 6 months of first onset of symptoms, and less marked when the patient was drowsy or se- dated. 5 The asynchronous EEG may be later replaced by multifocal epilcptiform abnormalities. Aminoff has described char- acteristic changes in electro-diagnosis of holoprosencephaly and Aicardi syndrome. 6 In both our patients with Aicardi syndrome it was indeed the characteristic asynchro- nous burst suppression pattern which ini- tially suggested the diagnosis and was later confirmed by ophthalmic and radioimaging techniques. Similarly Case 2 of hol- oprosencephaly was also suspected from the EEG record, hence the EEG appears to be highly specific, 30% of severe hol- oprosencephaly may be unassociated with facial abnormalities t and in such cases EEG would be an important tool in the diagnosis.

1. Volpe JJ. Neurology of the Newborn. Philadelphia: W.B. Saunders, 1987 : 22-25.

2. DeMyer W, White PT. EEG in hol- opro~ncephaly (Arrhinencephaly) Arch

,d~e,,,:ot 1964, t z : 507-520. 3. N'eitlich JA, Nussbaum RL, Packer RJ et

al. Heterogenity of clinical severity and molecular lesions in Aicardi syndrome. ] Paediatr 1990; 116 : 911-917.

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4.

5.

TIlE INDIAN JOURNAL OF PEDIATRICS

Dennis J, Bower BD. Aicardi syndrome. Dev Med Child Neurol 1972; 4 : 382-390. FarieUo RG, Chun R, Doro JM et at. EEG recognition of Aicardi syndrome.

Vol. 59, No. 1

6. Arch Neurol 1977; 34 : 563-566. Aminoff MJ. ElecmodiagT~osis in Child- hood Neurology. New York : Churchill Livingstone 1986; 96-97.

SHOES FOR CHILDREN

Optimum foot development r in the barefoot environmcnt. Shoes selection for children should be based on the barefoot model. The primary role of shoes is to protect the foot from injury and infection. The criteria to achieve the most effective footwear should be:

1. Quadrangular. To conform to the normal foot configuration, with abundant space for the toes.

2. Flexible. To allow free foot movement.

3. Flat. Without elevation of the hcel.

4. Porus. Uppers should be made of leather or unsealed fabric to avoid skin maceration or fungal infections.

5. Moderately tractive. Sole friction should be equivalent to that of the bare foot. Soles that are slippery (leather) or that create excessive friction (some rubber soles) should be avoided.

6. Light weight. To reduce cnergy expenditure.

7. Extended above the ankle. In the toddler to prevent the shoc from slipping off during running.

8. Acceptable. In appearance because children are very sensitive about that.

"Tennis shoes" arc commonly recommended for children. Unfortunately, "tennis shoes" cncompass a large variety of shoe types. Some arc ideal, meeting the criteria pcrfectly, whilc others have stiff soles with occlusive uppers. Physicians should describe the characteristics of a good shoe to the parents rather than simply recommending "tennis shoes".

Absracted from :

Lynn T, Staheli MD. Pediatrics-lndianEdition September 1991; Vol. 3, No. 5.508.