- Email: [email protected]
Serial IMP-SPECT and EEG studies in an infant with hemimegalencephaly
ELSEVIER
Brain & Development 1994; 16:475-9
Case report
Serial IMP-SPECT and EEG studies in an infant with hemimegalencephaly Tetsuzo Tagawa a, Kazumasa Otani a, Yasuyuki Futagi a, Akatsuki Wakayama b, Kazuyoshi Morimoto b, Yoshiki Morita c a Division of Pediatric Neurology, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka, Japan b Department of Neurosurgery, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka, Japan c Department of Pediatrics, Sakai Municipal Hospital, Sakai, Osaka, Japan
Received 22 November 1993; accepted 23 August 1994
An 8-month-old girl of hypomelanosis of Ito associated with hemimegalencephaly had frequent seizures beginning 44 h after birth. The seizures were secondarily generalized or unilateral initially, followed by infantile spasms at about 1.5 months of age. Frequent partial seizures appeared at 4 months of age. [~23I]N-Isopropyl-piodoamphetamine (IMP) single photon emission computed tomography (SPECT) was performed serially during an interictal period at 1, 3 and 7 months of age. At 1 and 3 months, IMP-SPECT showed a marked increase of IMP uptake in the pathological left hemisphere and electroencephalography (EEG) revealed left-sided dominant hypsarrhythmia. At 7 months of age, a reversal was seen, there being decreased uptake on SPECT in the pathological hemisphere and abundant high amplitude background activity mingled with epileptic discharges on EEG in the non-pathological hemisphere. These serial changes of IMP uptake on SPECT seemed to reflect either changes in epileptic activity or maturational changes in cerebral perfusion in hemimegalencephaly. Keywords: H e m i m e g a l e n c e p h a l y ; H y p o m e l a n o s i s o f Ito; S P E C T ; I n t r a c t a b l e epilepsy; A s y m m e t r i c h y p s a r r h y t h m i a ;
Cerebral perfusion
1. I N T R O D U C T I O N Hemimegalencephaly is a rare cerebral malformation consisting of enlargement of one hemisphere. It is frequently associated with early onset intractable seizures, developmental delay and contralateral hemiparesis. The seizures are often resistant to vigorous anti-epileptic therapies. Recently, hemispherectomy was found to improve the prognosis for this cerebral malformation [1-4]. Positron emission tomography (PET) or single photon emission computed tomography (SPECT) are important methods for functional, presurgical evaluation. Although studies involving PET [5] or SPECT [1,4,6] have been performed in hemimegalencephaly, there have been few serial studies concerning the relationship
Correspondence address: T. Tagawa, MD, Department of Pediatrics, Osaka Kouseinenkin Hospital, 4-2-78 Fukushima, Osaka, Japan 553. Fax: (81) (6) 445-8900.
0387-7604/94/$07.00 © 1994 Elsevier Science B.V. All rights reserved SSDI 0387-7604(94)00085-9
between structural abnormalities, functional imaging and epileptogenesis. [lz3I]N-isopropyl-p-iodoamphetamine (IMP) SPECT has recently become available for assessing cerebral perfusion in children with various brain disorders [7-10]. Previous studies have demonstrated its usefulness in partial or focal epilepsies. In this study, SPECT and E E G were performed serially from 1 to 7 months in a case of hypomelanosis of Ito associated with hemimegalencephaly, and changes at different ages were demonstrated.
2. C A S E R E P O R T A female infant was the product of a normal term pregnancy and delivery. Birth weight was 3170 g, and her head circumference was 36 cm ( + 2 S.D.). The family history was non-contributory. At 44 h after birth, generalized clonic convulsions developed, followed by right unilateral convul-
476
Tagawa, T. et al. /Brain & Development 1994; 16:47_5-9
Fig. 1. Magnetic resonance imaging of the brain. A: a Tl-weighted image (TR 400, TE 13) shows diffuse enlargement of the left hemisphere and dilatation of the left lateral ventricle. B: A T2-weighted image (TR 3000, TE 90) shows the markedly thickened cortex and pachygyria of the left cerebral hemisphere.
sions several hours later. H e r convulsions were successfully treated with diazepam and phenobarbital. She was transferred to the Osaka Medical Center and Research Institute for Maternal and Child Health at 1 month of age. At the time of admission, slight bulging of the left frontal area was noted. A depigmented nevus was evident on her left shoulder, which extended in a linear fashion to the flexion side of the left upper extremity. A diagnosis of hypomelanosis of Ito was made on a skin histological study [11]. Partial depigmentation was observed in the left iris. Funduscopic examination revealed no abnormalities. She was hemiparetic and tendon reflexes were brisker on the right than the left. No nystagmus or signs of posterior fossa disease were noted. Somatic hemihypertrophy was not present. Computed tomography (CT) demonstrated diffuse enlargement of the left hemisphere and dilatation of the left lateral ventricle. No abnormal enhancement was noted after contrast infusion. Diffuse, unilateral, hemispheric hypertrophy, left lateral ventricular enlargement, a pachygyric appearance, and heterotopic grey matter within the left frontal subcortical white matter were demonstrated by magnetic resonance imaging (MRI) (Fig. 1). At 1.5 months of age, asymmetrical infantile spasms became apparent and valproic acid was given. At 4 months of age, she began to suffer from frequent partial seizures. I M P - S P E C T was performed during an interictal period at 1, 3 and 7 months of age (Fig. 2). A diffuse increase in tracer uptake was demonstrated at 1 and 3 months of age, whereas there
was decreased uptake at 7 months of age in the pathological hemisphere, compared to in the contralateral hemisphere. All E E G recordings were performed within several hours after S P E C T measurements. E E G revealed left-sided dominant hypsarrhythmia at 1 month of age (Fig. 3), and almost continuous high voltage irregular slow waves intermingled with multifocal spikes in the pathological hemisphere at 3
Fig. 2. IMP-SPECT reveals a diffuse increase in tracer uptake at 1 and 3 months of age, but decreased uptake at 7 months of age in the pathological hemisphere.
477
Tagawa, T. et aL / Brain & Development 1994; 16:475-9 ,'r/r'~"]fI-;l~.-~-,'I
~
.... ~
~
~ .i~
Ur
F,-C,J"..IY.!.I'~/X 4~\(v~'X/~\FYYIv" ~ ,:,,-o,
'
~I
-
A'
_
,,,-%V " ' ' A ^
'
"~ V ~
'
v
~
"
/~ :
,W',k/% ',?,
",
"~
~
" ~'
....
=lI~
u-";V!Y"~-',I~--'~ A'.W
"~J~"
,
"
\/
,
,W;.u"., ^
'
'.
~
,"
d ~
,
I~,/
,
jv
,
SOuV
[
_
1
,
_
SEC
Fig. 3. Electroencephalography at 1 month of age.
months of age. Later, however, epileptic abnormalities spread to involve the contralateral hemisphere, and the frequency of epileptic discharges and amplitude of the background activity were paradoxically lower in the pathological hemisphere by 7 months old (Fig. 4).
3. D I S C U S S I O N Recently, PET or SPECT became available for evaluating the cerebral function in children and adults with various
OI'A1S\,
'~A,n,, / , '?u i!: ",-'~ ,, i&/
types of epilepsies. Previous studies generally demonstrated that the uptake of the radioisotope decreased during an interictal period and increased during an ictal period at the epileptic focus. In a case of a developmental malformation of the brain, ictal SPECT provided functional evidence for localized epileptogenesis [12]. There have been a few studies on cerebral metabolism or perfusion in hemimegalencephaly [4,5,6,13]. Twelve patients with unilateral megalencephaly were studied as to cerebral metabolism or perfusion using a radi'onuclide (Table 1). Mikhael and Matter found increased arterial flow in the megalencephalic hemisphere in an infant
': ,, ,,',t,v , \4~
~
,p,, ,,
/' _ ,,
FpPA2 C4"A2/
T4"Az
~
;
?'
....
f" i d
,;
...... ,,'
Fig. 4. Electroencephalography at 7 months of age.
' J~
"
kP, I"
L
478
Tagawa, T. et al. /Brain & Development 1994; 16." 475-9
Table 1 Reported results of cerebral blood flow or metabolism in hemimegalencephaly Authors
Patient's age Method
Michael et al. [13] 1.2.5 weeks Konkol et al. [6] 1.4y llm 2. 6y4m Chiron et al. [4] 1. lm 1.7m 1. 10m Rintahaka et al. [5] 1.20m 2. 34m 3.41m 4.5m 5.2m 6. 2m 7.9m 8.15m
Finding
Tc99mRN IMP-SPECT IMP-SPECT Xe-SPECT Xe-SPECT Xe-SPECT
Increased arterial flow Hypoperfusion Hypoperfusion Ictal hyperperfusion Hypoperfusion Hypoperfusion
FDG-PET FDG-PET FDG-PET FDG-PET FDG-PET FDG-PET FDG-PET FDG-PET
Hypometabolism Hypometabolism Hypermetabolism Hypometabolism Hypermetabolism Hypermetabolism Hypometabolism Hypometabolism
aged 2.5 weeks, in a dynamic radionuclide study [13]. Chiron et ai. found a 40% increase in regional cerebral blood flow (rCBF) in the pathological hemisphere during an ictal period with subcontinuous E E G discharges, using 133Xe SPECT [4]. Rintahaka et al. found interictal hypermetabolism in 3 of 8 patients with hemimegalencephaly, using PET [5]. One of them had an extensive heterotopic neuronal malformation with increased glucose utilization. In another 2 patients, the biochemical basis of the interictal hypermetabolism was thought to be probably related to increased energy consumption by an active epileptogenic focus [5,14]. The rest of the reported cases were found to have either hypometabolism or hypoperfusion. All the patients who showed either hypermetabolism or hyperperfusion, except one (Rintahaka's Case 3), were under 3 months of age. In the present patient, cerebral perfusion was found to be increased interictally in the pathological hemisphere at 1 and 3 months of age, compared to that on the contralateral side. rCBF is known to be increased both during and immediately after seizures [15], and to be decreased between seizures. No seizure was observed clinically in our patient, either during or immediately before the SPECT measurements. Since EEG could not be performed during the SPECT measurements, it remains a possibility that subclinical, electrical seizures could have occurred during or immediately before the SPECT measurements. It seems, however, unlikely that two independent SPECT measurements were performed under similar conditions at both 1 and 3 months of age. Interictal focal hyperperfusion or hypermetabolism has been demonstrated in patients with partial epilepsy by several groups [16-19]. IMP-SPECT can reveal increased perfusion in epileptic loci in the presence of focal electrical discharges, even in the absence of clinical seizures [20]. Therefore, both frequent clinical seizures and frequent interictal epileptiform activity could be associated with hyperperfusion in the epileptogenic focus. The hypoperfusion in the pathological hemisphere after 7 months of age found in both the present and reported patients may be the result of neuronal dysfunction. Electrophysiological [21] and pathological studies demonstrated the absence of normal cortical lamination in hemimegalencephaly and this absence might result in severe neuronal
dysfunction. Konkol et al. speculated that the main determinant of an abnormality of blood flow/metabolism observed on SPECT appeared to be the degree of functional disturbance due to cerebral dysplasia [6]. Thus, the serial changes in cerebral perfusion with age in infancy seem to reflect the functional fluctuation of epileptic foci. Another factor causing serial changes in cerebral perfusion is maturational changes [22,23]. Because the present IMP-SPECT study just provided the relative distribution of rCBF, the changes in the present patient might have resulted from maturational changes in the contralateral hemisphere. As cortical perfusion increases in the contralateral intact hemisphere during maturation, the relative hypoperfusion progresses in the pathological hemisphere compared with the perfusion in the intact hemisphere, even when the absolute perfusion is constant. EEG and SPECT are valuable methods for evaluation of the cerebral function in patients with cerebral malformations. The results obtained using these methods could be useful for assessing functional abnormalities and deciding the clinical management. The evolutionary changes of SPECT findings with the course of epilepsy could provide important information on the evolution of epileptogenesis.
REFERENCES 1. King M, Stephenson JBP, Ziervogel M, Doyle D, Galbraith S. Hemimegalencephaly: a case for hemispherectomy? Neuropediatrics 1985; 16: 46-55. 2. Vigevano F, Bertini E, Boldrini R, et al. Hemimegalencephaly and intractable epilepsy: benefits of hemispherectomy. Epilepsia 1989; 30: 833-43. 3. Vigevano F, di Rocco C. Effectiveness of hemispherectomy in hemimegalencephaly with intractable seizures. Neuropediatrics 1990; 21: 222-3. 4. Chiron C, Raynaud C, Jambaque I, Dulac O, Zilbovicius M, Syrota A. A serial study of regional cerebral blood flow before and after hemispherectomy in a child. Epil Res 1991; 8: 232-40. 5. Rintahaka PJ, Chugani HT, Messa C, Phelps ME. Hemimegalencephaly: evaluation with positron emission tomography. Pediatr Neurol 1993; 9: 21-8. 6. Konkol RJ, Maister BH, Wells RG, Sty JR. Hemimegalencephaly: clinical, EEG, neuroimaging, and IMP-SPECT correlation. Pediatr Neurol 1990; 6: 414-8. 7. Flamini JR, Konkol RJ, Wells RG, Sty JR. 1-123 iofetamine SPECT scan in children with neurological disorders. Wis Med J 1990; 89: 584-7. 8. livanainen M, Launes J, Pihko H, Nikkinen P, Lindroth L. Single-photon emission computed tomography of brain perfusion: analysis of 60 paediatric cases. Dev Med Child Neurol 1990; 32: 63-8. 9. Uvebrant P, Byure J, Hedstrom A, Ekholm S. Brain single photon emission computed tomography (SPECT) in neuropediatrics. Neuropediatrics 1991; 22: 3-9. 10. Vies JSH, Demandt E, Ceulemans B, de Roo M, Casaer PJM. Single photon emission computed tomography (SPECT) in seizure disorders in childhood. Brain Dec (Tokyo) 1990; 12: 385-9. II. Tagawa T, Otani K, Futagi Y, et al. Hypomelanosis of Ito associated with hemimegalencephaly (in Japanese). No To Hattatsu (Tokyo), accepted. 12. Kuzniecky R, Mountz JM, Wheatley G, Morawetz R. Ictal single-photon emission computed tomography demonstrates Io-
Tagawa, T. et al. /Brain & Development 1994; 16. 475-9
13.
14.
15.
16.
17.
18.
calized epileptogenesis in cortical dysplasia. Ann Neurol 1993; 34: 627-31. Mikbael MA, Matter AG. Malformation of the cerebral cortex with heterotopia of the grey matter. J Comput Assist Tomogr 1978; 2: 291-6. Chugani HT, Shewmon DA, Khanna S, Phelps ME. Interictal and postictal focal hypermetabolism on positron emission tomography. Pediatr Neurol 1993; 9: 10-5. Rowe CC, Berkovic SF, Benjamin Sia ST, et al. Localization of epileptic foci with postictal single photon emission computed tomography. Ann Neurol 1989; 26: 660-8. Lee BI, Markand ON, Siddiqui AR, et al. Single photon emission computed tomography (SPECT) brain imaging using N, N, N'-trimetbyl-N'-(2-hydroxy-3-methyl-5-123I-iodobenzyl)- 1,3propanediamine 2 HCI (HIPDM): intractable complex partial seizures. Neurology 1986; 36: 1471-7. Denays R, Rubinstein M, Ham H, Piepsz A, Noel P. Single photon emission computed tomography in seizure disorders. Arch Dis Child 1988; 63: 1184-8. Abdel-Dayem HM, Nawaz MK, Hassoon MM, Abdel-Rahman
19.
20.
21.
22.
23.
479
M, Olofsson OE. Cerebral perfusion abnormalities in therapy-resistant epilepsy in mentally retarded pediatric patients. Comparison between EEG, X-ray CT, and Tc-99m HMPAO. Clin Nucl Med 1991; 16: 557-61. Kawamura M, Murase K, Kataoka M, et al. Early and delayed 1-123 IMP SPECT in epileptic patients with partial seizures and normal CT. Clin Nucl Med 1991; 16: 839-46. Biersack HJ, Reichmann K, Winkler C, et al. 99roTe-labelled hexamethylpropyleneamine oxime photon emission scans in epilepsy. Lancet 1985; Dec 21/28: 1436-7. Di Capua M, Vigevano F, Wisniewski K. Somatosensory evoled potentials in hemimegalencephaly and lissencephaly: anatomofunctional correlations. Brain Dev (Tokyo) 1993; 15: 253-7. Rubinstein M, Denays R, Ham HR, et al. Functional imaging of brain maturation in humans using iodine-123 iodoamphetamine and SPECT. J Nucl Med 1989; 30: 1982-5. Chiron C, Raynaud C, Masiere B, et al. Changes in regional cerebral blood flow during brain maturation in children and adolescents. J Nucl Med 1992; 33: 696-703.
Brain & Development 1994; 16:475-9
Case report
Serial IMP-SPECT and EEG studies in an infant with hemimegalencephaly Tetsuzo Tagawa a, Kazumasa Otani a, Yasuyuki Futagi a, Akatsuki Wakayama b, Kazuyoshi Morimoto b, Yoshiki Morita c a Division of Pediatric Neurology, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka, Japan b Department of Neurosurgery, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka, Japan c Department of Pediatrics, Sakai Municipal Hospital, Sakai, Osaka, Japan
Received 22 November 1993; accepted 23 August 1994
An 8-month-old girl of hypomelanosis of Ito associated with hemimegalencephaly had frequent seizures beginning 44 h after birth. The seizures were secondarily generalized or unilateral initially, followed by infantile spasms at about 1.5 months of age. Frequent partial seizures appeared at 4 months of age. [~23I]N-Isopropyl-piodoamphetamine (IMP) single photon emission computed tomography (SPECT) was performed serially during an interictal period at 1, 3 and 7 months of age. At 1 and 3 months, IMP-SPECT showed a marked increase of IMP uptake in the pathological left hemisphere and electroencephalography (EEG) revealed left-sided dominant hypsarrhythmia. At 7 months of age, a reversal was seen, there being decreased uptake on SPECT in the pathological hemisphere and abundant high amplitude background activity mingled with epileptic discharges on EEG in the non-pathological hemisphere. These serial changes of IMP uptake on SPECT seemed to reflect either changes in epileptic activity or maturational changes in cerebral perfusion in hemimegalencephaly. Keywords: H e m i m e g a l e n c e p h a l y ; H y p o m e l a n o s i s o f Ito; S P E C T ; I n t r a c t a b l e epilepsy; A s y m m e t r i c h y p s a r r h y t h m i a ;
Cerebral perfusion
1. I N T R O D U C T I O N Hemimegalencephaly is a rare cerebral malformation consisting of enlargement of one hemisphere. It is frequently associated with early onset intractable seizures, developmental delay and contralateral hemiparesis. The seizures are often resistant to vigorous anti-epileptic therapies. Recently, hemispherectomy was found to improve the prognosis for this cerebral malformation [1-4]. Positron emission tomography (PET) or single photon emission computed tomography (SPECT) are important methods for functional, presurgical evaluation. Although studies involving PET [5] or SPECT [1,4,6] have been performed in hemimegalencephaly, there have been few serial studies concerning the relationship
Correspondence address: T. Tagawa, MD, Department of Pediatrics, Osaka Kouseinenkin Hospital, 4-2-78 Fukushima, Osaka, Japan 553. Fax: (81) (6) 445-8900.
0387-7604/94/$07.00 © 1994 Elsevier Science B.V. All rights reserved SSDI 0387-7604(94)00085-9
between structural abnormalities, functional imaging and epileptogenesis. [lz3I]N-isopropyl-p-iodoamphetamine (IMP) SPECT has recently become available for assessing cerebral perfusion in children with various brain disorders [7-10]. Previous studies have demonstrated its usefulness in partial or focal epilepsies. In this study, SPECT and E E G were performed serially from 1 to 7 months in a case of hypomelanosis of Ito associated with hemimegalencephaly, and changes at different ages were demonstrated.
2. C A S E R E P O R T A female infant was the product of a normal term pregnancy and delivery. Birth weight was 3170 g, and her head circumference was 36 cm ( + 2 S.D.). The family history was non-contributory. At 44 h after birth, generalized clonic convulsions developed, followed by right unilateral convul-
476
Tagawa, T. et al. /Brain & Development 1994; 16:47_5-9
Fig. 1. Magnetic resonance imaging of the brain. A: a Tl-weighted image (TR 400, TE 13) shows diffuse enlargement of the left hemisphere and dilatation of the left lateral ventricle. B: A T2-weighted image (TR 3000, TE 90) shows the markedly thickened cortex and pachygyria of the left cerebral hemisphere.
sions several hours later. H e r convulsions were successfully treated with diazepam and phenobarbital. She was transferred to the Osaka Medical Center and Research Institute for Maternal and Child Health at 1 month of age. At the time of admission, slight bulging of the left frontal area was noted. A depigmented nevus was evident on her left shoulder, which extended in a linear fashion to the flexion side of the left upper extremity. A diagnosis of hypomelanosis of Ito was made on a skin histological study [11]. Partial depigmentation was observed in the left iris. Funduscopic examination revealed no abnormalities. She was hemiparetic and tendon reflexes were brisker on the right than the left. No nystagmus or signs of posterior fossa disease were noted. Somatic hemihypertrophy was not present. Computed tomography (CT) demonstrated diffuse enlargement of the left hemisphere and dilatation of the left lateral ventricle. No abnormal enhancement was noted after contrast infusion. Diffuse, unilateral, hemispheric hypertrophy, left lateral ventricular enlargement, a pachygyric appearance, and heterotopic grey matter within the left frontal subcortical white matter were demonstrated by magnetic resonance imaging (MRI) (Fig. 1). At 1.5 months of age, asymmetrical infantile spasms became apparent and valproic acid was given. At 4 months of age, she began to suffer from frequent partial seizures. I M P - S P E C T was performed during an interictal period at 1, 3 and 7 months of age (Fig. 2). A diffuse increase in tracer uptake was demonstrated at 1 and 3 months of age, whereas there
was decreased uptake at 7 months of age in the pathological hemisphere, compared to in the contralateral hemisphere. All E E G recordings were performed within several hours after S P E C T measurements. E E G revealed left-sided dominant hypsarrhythmia at 1 month of age (Fig. 3), and almost continuous high voltage irregular slow waves intermingled with multifocal spikes in the pathological hemisphere at 3
Fig. 2. IMP-SPECT reveals a diffuse increase in tracer uptake at 1 and 3 months of age, but decreased uptake at 7 months of age in the pathological hemisphere.
477
Tagawa, T. et aL / Brain & Development 1994; 16:475-9 ,'r/r'~"]fI-;l~.-~-,'I
~
.... ~
~
~ .i~
Ur
F,-C,J"..IY.!.I'~/X 4~\(v~'X/~\FYYIv" ~ ,:,,-o,
'
~I
-
A'
_
,,,-%V " ' ' A ^
'
"~ V ~
'
v
~
"
/~ :
,W',k/% ',?,
",
"~
~
" ~'
....
=lI~
u-";V!Y"~-',I~--'~ A'.W
"~J~"
,
"
\/
,
,W;.u"., ^
'
'.
~
,"
d ~
,
I~,/
,
jv
,
SOuV
[
_
1
,
_
SEC
Fig. 3. Electroencephalography at 1 month of age.
months of age. Later, however, epileptic abnormalities spread to involve the contralateral hemisphere, and the frequency of epileptic discharges and amplitude of the background activity were paradoxically lower in the pathological hemisphere by 7 months old (Fig. 4).
3. D I S C U S S I O N Recently, PET or SPECT became available for evaluating the cerebral function in children and adults with various
OI'A1S\,
'~A,n,, / , '?u i!: ",-'~ ,, i&/
types of epilepsies. Previous studies generally demonstrated that the uptake of the radioisotope decreased during an interictal period and increased during an ictal period at the epileptic focus. In a case of a developmental malformation of the brain, ictal SPECT provided functional evidence for localized epileptogenesis [12]. There have been a few studies on cerebral metabolism or perfusion in hemimegalencephaly [4,5,6,13]. Twelve patients with unilateral megalencephaly were studied as to cerebral metabolism or perfusion using a radi'onuclide (Table 1). Mikhael and Matter found increased arterial flow in the megalencephalic hemisphere in an infant
': ,, ,,',t,v , \4~
~
,p,, ,,
/' _ ,,
FpPA2 C4"A2/
T4"Az
~
;
?'
....
f" i d
,;
...... ,,'
Fig. 4. Electroencephalography at 7 months of age.
' J~
"
kP, I"
L
478
Tagawa, T. et al. /Brain & Development 1994; 16." 475-9
Table 1 Reported results of cerebral blood flow or metabolism in hemimegalencephaly Authors
Patient's age Method
Michael et al. [13] 1.2.5 weeks Konkol et al. [6] 1.4y llm 2. 6y4m Chiron et al. [4] 1. lm 1.7m 1. 10m Rintahaka et al. [5] 1.20m 2. 34m 3.41m 4.5m 5.2m 6. 2m 7.9m 8.15m
Finding
Tc99mRN IMP-SPECT IMP-SPECT Xe-SPECT Xe-SPECT Xe-SPECT
Increased arterial flow Hypoperfusion Hypoperfusion Ictal hyperperfusion Hypoperfusion Hypoperfusion
FDG-PET FDG-PET FDG-PET FDG-PET FDG-PET FDG-PET FDG-PET FDG-PET
Hypometabolism Hypometabolism Hypermetabolism Hypometabolism Hypermetabolism Hypermetabolism Hypometabolism Hypometabolism
aged 2.5 weeks, in a dynamic radionuclide study [13]. Chiron et ai. found a 40% increase in regional cerebral blood flow (rCBF) in the pathological hemisphere during an ictal period with subcontinuous E E G discharges, using 133Xe SPECT [4]. Rintahaka et al. found interictal hypermetabolism in 3 of 8 patients with hemimegalencephaly, using PET [5]. One of them had an extensive heterotopic neuronal malformation with increased glucose utilization. In another 2 patients, the biochemical basis of the interictal hypermetabolism was thought to be probably related to increased energy consumption by an active epileptogenic focus [5,14]. The rest of the reported cases were found to have either hypometabolism or hypoperfusion. All the patients who showed either hypermetabolism or hyperperfusion, except one (Rintahaka's Case 3), were under 3 months of age. In the present patient, cerebral perfusion was found to be increased interictally in the pathological hemisphere at 1 and 3 months of age, compared to that on the contralateral side. rCBF is known to be increased both during and immediately after seizures [15], and to be decreased between seizures. No seizure was observed clinically in our patient, either during or immediately before the SPECT measurements. Since EEG could not be performed during the SPECT measurements, it remains a possibility that subclinical, electrical seizures could have occurred during or immediately before the SPECT measurements. It seems, however, unlikely that two independent SPECT measurements were performed under similar conditions at both 1 and 3 months of age. Interictal focal hyperperfusion or hypermetabolism has been demonstrated in patients with partial epilepsy by several groups [16-19]. IMP-SPECT can reveal increased perfusion in epileptic loci in the presence of focal electrical discharges, even in the absence of clinical seizures [20]. Therefore, both frequent clinical seizures and frequent interictal epileptiform activity could be associated with hyperperfusion in the epileptogenic focus. The hypoperfusion in the pathological hemisphere after 7 months of age found in both the present and reported patients may be the result of neuronal dysfunction. Electrophysiological [21] and pathological studies demonstrated the absence of normal cortical lamination in hemimegalencephaly and this absence might result in severe neuronal
dysfunction. Konkol et al. speculated that the main determinant of an abnormality of blood flow/metabolism observed on SPECT appeared to be the degree of functional disturbance due to cerebral dysplasia [6]. Thus, the serial changes in cerebral perfusion with age in infancy seem to reflect the functional fluctuation of epileptic foci. Another factor causing serial changes in cerebral perfusion is maturational changes [22,23]. Because the present IMP-SPECT study just provided the relative distribution of rCBF, the changes in the present patient might have resulted from maturational changes in the contralateral hemisphere. As cortical perfusion increases in the contralateral intact hemisphere during maturation, the relative hypoperfusion progresses in the pathological hemisphere compared with the perfusion in the intact hemisphere, even when the absolute perfusion is constant. EEG and SPECT are valuable methods for evaluation of the cerebral function in patients with cerebral malformations. The results obtained using these methods could be useful for assessing functional abnormalities and deciding the clinical management. The evolutionary changes of SPECT findings with the course of epilepsy could provide important information on the evolution of epileptogenesis.
REFERENCES 1. King M, Stephenson JBP, Ziervogel M, Doyle D, Galbraith S. Hemimegalencephaly: a case for hemispherectomy? Neuropediatrics 1985; 16: 46-55. 2. Vigevano F, Bertini E, Boldrini R, et al. Hemimegalencephaly and intractable epilepsy: benefits of hemispherectomy. Epilepsia 1989; 30: 833-43. 3. Vigevano F, di Rocco C. Effectiveness of hemispherectomy in hemimegalencephaly with intractable seizures. Neuropediatrics 1990; 21: 222-3. 4. Chiron C, Raynaud C, Jambaque I, Dulac O, Zilbovicius M, Syrota A. A serial study of regional cerebral blood flow before and after hemispherectomy in a child. Epil Res 1991; 8: 232-40. 5. Rintahaka PJ, Chugani HT, Messa C, Phelps ME. Hemimegalencephaly: evaluation with positron emission tomography. Pediatr Neurol 1993; 9: 21-8. 6. Konkol RJ, Maister BH, Wells RG, Sty JR. Hemimegalencephaly: clinical, EEG, neuroimaging, and IMP-SPECT correlation. Pediatr Neurol 1990; 6: 414-8. 7. Flamini JR, Konkol RJ, Wells RG, Sty JR. 1-123 iofetamine SPECT scan in children with neurological disorders. Wis Med J 1990; 89: 584-7. 8. livanainen M, Launes J, Pihko H, Nikkinen P, Lindroth L. Single-photon emission computed tomography of brain perfusion: analysis of 60 paediatric cases. Dev Med Child Neurol 1990; 32: 63-8. 9. Uvebrant P, Byure J, Hedstrom A, Ekholm S. Brain single photon emission computed tomography (SPECT) in neuropediatrics. Neuropediatrics 1991; 22: 3-9. 10. Vies JSH, Demandt E, Ceulemans B, de Roo M, Casaer PJM. Single photon emission computed tomography (SPECT) in seizure disorders in childhood. Brain Dec (Tokyo) 1990; 12: 385-9. II. Tagawa T, Otani K, Futagi Y, et al. Hypomelanosis of Ito associated with hemimegalencephaly (in Japanese). No To Hattatsu (Tokyo), accepted. 12. Kuzniecky R, Mountz JM, Wheatley G, Morawetz R. Ictal single-photon emission computed tomography demonstrates Io-
Tagawa, T. et al. /Brain & Development 1994; 16. 475-9
13.
14.
15.
16.
17.
18.
calized epileptogenesis in cortical dysplasia. Ann Neurol 1993; 34: 627-31. Mikbael MA, Matter AG. Malformation of the cerebral cortex with heterotopia of the grey matter. J Comput Assist Tomogr 1978; 2: 291-6. Chugani HT, Shewmon DA, Khanna S, Phelps ME. Interictal and postictal focal hypermetabolism on positron emission tomography. Pediatr Neurol 1993; 9: 10-5. Rowe CC, Berkovic SF, Benjamin Sia ST, et al. Localization of epileptic foci with postictal single photon emission computed tomography. Ann Neurol 1989; 26: 660-8. Lee BI, Markand ON, Siddiqui AR, et al. Single photon emission computed tomography (SPECT) brain imaging using N, N, N'-trimetbyl-N'-(2-hydroxy-3-methyl-5-123I-iodobenzyl)- 1,3propanediamine 2 HCI (HIPDM): intractable complex partial seizures. Neurology 1986; 36: 1471-7. Denays R, Rubinstein M, Ham H, Piepsz A, Noel P. Single photon emission computed tomography in seizure disorders. Arch Dis Child 1988; 63: 1184-8. Abdel-Dayem HM, Nawaz MK, Hassoon MM, Abdel-Rahman
19.
20.
21.
22.
23.
479
M, Olofsson OE. Cerebral perfusion abnormalities in therapy-resistant epilepsy in mentally retarded pediatric patients. Comparison between EEG, X-ray CT, and Tc-99m HMPAO. Clin Nucl Med 1991; 16: 557-61. Kawamura M, Murase K, Kataoka M, et al. Early and delayed 1-123 IMP SPECT in epileptic patients with partial seizures and normal CT. Clin Nucl Med 1991; 16: 839-46. Biersack HJ, Reichmann K, Winkler C, et al. 99roTe-labelled hexamethylpropyleneamine oxime photon emission scans in epilepsy. Lancet 1985; Dec 21/28: 1436-7. Di Capua M, Vigevano F, Wisniewski K. Somatosensory evoled potentials in hemimegalencephaly and lissencephaly: anatomofunctional correlations. Brain Dev (Tokyo) 1993; 15: 253-7. Rubinstein M, Denays R, Ham HR, et al. Functional imaging of brain maturation in humans using iodine-123 iodoamphetamine and SPECT. J Nucl Med 1989; 30: 1982-5. Chiron C, Raynaud C, Masiere B, et al. Changes in regional cerebral blood flow during brain maturation in children and adolescents. J Nucl Med 1992; 33: 696-703.