A serial study of regional cerebral blood flow before and after hemispherectomy in a child

Epilepsy Res., 8 (1991) 232-240

232

Elsevier EPIRES 00387

A serial study of regional cerebral blood flow before and after hemispherectomy in a child

C. Chirona, C. Raynaudb, I. JambaquC”, 0. Dulaca, M. Zilboviciusb and A. Syrotab “Clinique de Pbdiatrie et de PuCriculture, INSERM

U29, H6pital Saint Vincent de Paul, Paris, and

bDSV, Service Hospitalier Frbdtric Joliot, Orsay (France)

(Revision received 10 October 1990 accepted 13 October 1990) Key words: Regional cerebral blood flow; Single photon emission computed tomography; Hemimegalencephaly;

Childhood epilepsy; Hemispherectomy

Hemimegalencephaly (HME) is a severe unilateral brain malformation the prognosis of which may be improved by hemispherectomy. HME also provides a unique opportunity to compare normal and pathological hemispheric function in the same patient. We performed a serial functional cerebral imaging study in a child suffering from a neuropathologically confirmed left HME. He was hemispherectomized at 11 months because of intractable epilepsy; this led to cessation of seizures and dramatic psychomotor improvement. Regional cerebral blood flow (rCBF) was studied at 1,7,10, 12 and 25 months with single photon computed tomography (SPECT) using 133-Xenon and with simultaneous EEG recording. At one month of age SPECT was performed ictally. During left EEG discharges, rCBF was 40% higher on the left hemisphere than on the right, even in occipital and frontal regions, usually immature at this age. A crossed cerebellar hyperperfusion was also found. At 7 and 10 months, SPECT was performed interictally; rCBF was 45% lower in the left hemisphere than in the right. During follow-up, global and regional CBF values showed normal levels and normal maturation in the right hemisphere except for a mild and transient decrease observed one month after hemispherectomy. SPECT provides an additional procedure for studying hemispheric function in vivo. Serial SPECT imaging may be useful for the preoperative and postoperative evaluation in unilateral cerebral malformation.

INTRODUCTION Hemimegalencephaly (HME) is a unilateral cerebral malformation that produces severe epilepsy, hemiplegia, and psychomotor impairmentz7. It provides a unique opportunity to compare normal and pathological hemispheric brain function in the same patient. Early diagnosis is possible using magnetic resonance imaging (MRI)” and progno-

Correspondence to: C. Chiron, 62 Avenue Denfert Rochereau, 75674 Paris Cedex 14, France.

0920-1211/91/$03.50~ 1991 Elsevier Science Publishers B.V.

sis may be improved by hemispherectomy6~‘7~31. Neurological improvement after hemispherectomy is related to the functional integrity of the contralateral hemisphere. Hemispheric function has been studied with prolonged electroencephalographic (EEG) recordings31 and with regional glucose metabolic rates measured by positron emission tomography (PET)6. Single photon emission computed tomography (SPECT) provides an additional method of functional evaluation which measures regional cerebral blood flow (rCBF) and is easy to perform and repeat in children4. In the present study we performed serial rCBF studies

Fig. 1. Magnetic resonance imaging (MRI). (A) 7 months. Tl weighted sequence. Axial slices. Left: normal whole cerebellum. Right: normal right hemisphere but left hemisphere exhibiting ah signs of hemimegalencephaly: hypertrophy of the hemisphere, thick cortical ribbon, and abnormal signal in the white matter. (B) 25 months. Tl weighted sequence. On the left, coronal slice, on the right, axial slice. Atrophy of the right cerebellar hemisphere, 1 year 4 months after left hemispherectomy.

234 using SPECT in a patient with HME in order to follow the rCBF changes in each hemisphere and in the cerebellum before and after hemispherectomy. CASE REPORT Our patient, a boy, was born after a 35week normal pregnancy and delivery. Because of major axial hypotonia, MRI was performed and showed an HME involving the entire left cerebral hemisphere (Fig. 1A). Epilepsy occurred at 3 weeks, with daily partial seizures related to left hemispheric discharges on the EEG. At 11 months, epilepsy remained intractable with more than 10 seizures a day and the patient exhibited right hemiplegia and severe axial hypotonia. The patient had achieved intermittent eye contact and left voluntary grasping, but not head control nor sitting. Because of severe epilepsy and a poor neurological condition, and because the right hemisphere was presumed to be normal according to MRI, EEG and SPECT follow-up data, left hemispherectomy was performed at 11 months, consisting of extrathalamic resection. Neuropathological examination which we reported elsewhere confirmed HME, and showed many giant neurons with a complex dendritic tree and hyperplasia of glial cells with giant astrocytes and proliferation of Rosenthal fibers*‘. After surgery, seizures disappeared completely and antiepileptic treatment was stopped at 15 months. The child achieved full head control at 14 months and sitting at 17 months. At 25 months, hemiplegia had decreased and the child was able to walk with aid but exhibited right dystonic grasping, hemianopsia and neglect. The first vocal sounds occurred 2 weeks after surgery and the first words at 17 months. At 25 months the child could speak approximately 10 words. METHODS rCBF was measured with a brain dedicated system, TOMOMATIC 564, using 133Xe.Five contiguous 2-cm slices were obtained, with an axial resolution of 14 mm. The ‘33Xe was delivered intravenously at doses of 2-2.5 mCi/kg. rCBF was calcu-

lated with the algorithm of Celsis* and the method was described and validated by Lassen’g~20*2’.The method was adapted to children replacing 133Xeinhalation by intravenous administration and by adding a premeditation to prevent any head movement. Premeditation consisted of rectal pentobarbital (5 mg/kg) and oral alimemazine (1 mg/kg). In a series of 37 children a slight effect of the tracer administration mode was found, the injection mode leading to rCBF values 10% higher than the inhalation mode, but this effect was not considered significant23. The effect of premedication was not found to be significant in a group of 13 children studied before and after premeditation in our department. The residual error, or accuracy, of an rCBF measurement in children, was 7.5% and was independent of the region23. The radiation dose to the lung considered as the target organ was assessed to be approximately 300 to 400 mrads in adults’*,“. This was adapted to children by Kellershohn using Powsne? and Documenta Geigy’ and calculated to be 260 and 270 mrads in newborns and children aged 5 years with an administered dose of 2.5 and 2 mCi/kg, respectively16. The gonadal dose is negligible with ‘33Xe. The 5 slices obtained were parallel to the orbitomeatal (OM) plane and they were centered on the planes OM, OM +20, +40, +60, and +80 mm. rCBF was measured on 20 symmetrical cortical regions of interest (ROT) per slice, ranging from 1.5-3 cm* in size. ‘Slice CBF’ was calculated for both sides on each slide. Global CBF was calculated for each hemisphere from the 3 ‘slice CBF’ including most of the cortex, i.e., levels OM +40, +60, +80. Regional CBFs were calculated in 5 cortical regions on each side and represented the sensorimotor, the occipital, the paramedian frontal, the posterior temporal and the cerebellar cortex. rCBF was measured by SPECT 3 times before surgery (at 1, 7, and 10 months) and twice after surgery (at 12 and 25 months) (Fig. 2). SPECT studies were performed with the informed consent of the child’s parents. MRI was performed at the same age as SPECT, twice before surgery (at 1 and 7 months) (Fig. 1A) and once afterwards (25 months) (Fig. 1B). EEG and SPECT studies were carried out simultaneously before surgery.

235

LEFT HEMIMEGALENCEPHALY 1M

7M

12M

25M

OM

+ 60

+ 80 Fig. 2. Serial regional cerebral blood flow (rCBF) imaging. rCBF imaging by single photon emission computed tomography (SPECT) using 133-Xenon was performed at 1,7,12, and 25 months. rCBF was measured on 5 slices, parallel to the orbito-meatal (OM) plane, at levels OM, +20, +40, +60, and +80 mm. Black and white intensity correspond to the measure of rCBF in ml/l00 g/mn (see text). The l-month and 7-month studies were performed preoperatively; the 1Zmonth and 25 month studies were performed after left hemispherectomy. The l-month study was performed ictally, the others interictally. At 1 month rCBF was normal in the right cerebral hemisphere and high on the left (OM +20, +40, +60, +80); on the contrary, rCBF was high in the right cerebellar hemisphere (OM). At 7 months rCBF was low in the left cerebral hemisphere and normal in the right. At 12 and 25 months rCBF was very low in the left side (OM +20, +40, +60, +80) whereas it exhibited a normal pattern according to age in the right cerebral hemisphere. Cerebellar rCBF was symmetrical at 12 months but was diminished on the right at 25 months (OM).

RESULTS

At 7 and 10 months, rCBF studies were performed interictally. Global CBF was 47% and 37% lower, respectively, in the pathological hemisphere than in the normal hemisphere, and the decrease involved the entire hemisphere. After hemispherectomy, the global CBF was 80% and 60% lower on the left side than on the right at 12 months and 25 months, respectively. At 12 months all rCBFs were very low as expected, but at 25 months it was evident that only the paramedian frontal region showed a high rCBF value, resulting in an apparent increase in the global CBF. As shown by MRI, this resulted from the displacement of the remaining right frontal lobe into the left cavity. The non-malformed

hemisphere

(Fig. 2 and Table

I)

During follow-up, the global CBF as well as the 4 rCBFs of the right hemisphere increased progressively, according to the curves obtained in controls during the first two years of life (Fig. 3A and B). Only moderate and temporary discrepancies were observed in the examination performed 1 month after hemispherectomy, in which global CBF decreased by 10%. The cerebellum (Fig. 2 and Table I)

At 1 month, during left cerebral hemispheric discharges, cerebellar hemispheric rCBF was 30% higher on the right side than on the left. But at 7 and 10 months, in an interictal period, no rCBF difference was found between cerebellar hemispheres, which were symmetrical and of normal size on MRI (Fig. 1A). One month after surgery, rCBF remained the same in both cerebellar hemispheres, but 13 months later it had decreased by 33% in the right cerebellar hemisphere compared to the left side. In accordance with these findings, the right cerebellar hemisphere was clearly reduced in size and showed signs of atrophy on the MRI performed at that time (Fig. 1B).

The malformed hemisphere (Fig. 2 and Table I)

At 1 month, global CBF of the malformed hemisphere was 40% higher than in the normal hemisphere. Study was performed during an ictal period with subcontinuous left EEG discharges. The increase involved every regional CBF.

DISCUSSION A4ethodologicalproblems

The method used to measure rCBF has already been described and validated in adults’g,20*21.Cor-

236 TABLE I Mean cerebral bloodflow data (mlllO0 glmin) m, months; OM, orbito-meatal; bide.

Mean global CBF left right Mean slice CBF OM +40 left right OM +60 left right OM +80 left right Mean regional CBF sensorimotor left right occipital left right paramedian frontal left right posterior temporal left right cerebellar hemisphere left right Antiepileptic drugs

CBF, cerebral blood flow; VPA, valproate; PB, phenobarbital;

CBZ, carbamazepine;

PG, proga-

lm

7m

1Om

12m

25m

66 47

31 58

41 65

12 58

28 68

65 44

37 60

45 69

16 60

25 68

66 49

30 58

43 65

10 51

25 65

26 57

35 60

10 58

33 70

68 41

32 66

44 65

11 80

12 62

69 41

31 69

41 79

6 70

13 71

54 36

21 52

34 57

9 50

48 59

71 30

31 67

43 69

8 77

10 15

61 80

55 57

51 57

65 69

72 48

VPA

PB. CBZ. PG

PB. CBZ. PG

CBZ. PG

None

tical rCBF values obtained by SPECT using ‘33Xe and by PET using continuous inhalation of “CO, in the same patients are significantly correlatedz6. Adaptation of the SPECT technique to infants implied two modifications: intravenous (iv.) injection of ‘33Xe instead of inhalation, and the use of premeditation; we found no significant rCBF changes. Because SPECT is easy to perform, requires no blood sampling and the radiation dose is low (250 mCi/examination), serial studies may be performed in the same patient. As data acquisition only takes 5 min, ictal studies are also possible.

Regional hypoperfusion observed in our patient cannot be related to antiepileptic drugs (AED) because the changes they produce in CBF and metabolism involve the entire brain without unilateral defects29. In addition, our results show that AEDs did not affect the normal cortical maturation, although they had been administered from birth, and that stopping AEDs did not modify the maturational rCBF pattern. rCBFfindings

in the pathological hemisphere

In a previous series of 6 HME children, we re-

237

A

L@JT Side (pathological side)

Mean CBF

aloHTside (normalside)

(mlhntVlO0g)

__.

100

ICTAL

1

B

INTERICTAL

7

10

12

loo 80

25

Months

8E~8o~1-uoro~com~~

* . I--

occtPtTMcomEx

rwozs la0

CONTROL

Fig. 3. (A) Longitudinal pattern of mean global CBF in the left and right sides compared to that of control patients (expressed in ml/l00 g/min). (B) Longitudinal pattern of mean regional CBFs in the normal right side compared to that of control patients (expressed as a percentage of the mean global CBF).

fl

fi

* .

CWOG l -T;

‘To

I I

t

I

4

a,,

011a4

0 control patients 4 Present patient (on the right ride, normal ride)

a

8

10 12

l@

a

’

238 ported a marked hypoperfusion in the malformed brain cortex3. In the present case, neuropathological examination revealed a number of giant neurons with a disorganized dendritic tree**, suggesting neuronal dysfunction to be the cause of hypoperfusion. Our results show that the malformed cortex is also able to increase CBF ictally. PET studies previously found an increase in rCBF during seizures, associated with metabolic hyperactivitylO,“. Our data suggest that rCBF regulation is preserved, even in severe hemispheric malformation. On our first SPECT study, performed at birth, it is clear that rCBF rise during ictal discharge in regions that are not mature at this age’; frontal and occipital areas of the malformed side exhibit a rCBF pattern usually observed after 9 months of age3’. rCBFfindings

in the normal hemisphere

Prognosis and therefore a decision on hemispherectomy depend on the functional integrity of the non-malformed hemisphere. Function may be affected by malformative or by acquired lesions. First of all, heterotopias of abnormal neurons have been described in the side presumed norma127, but clinical and radiological examinations often fail to reveal them. They may induce seizures in the side presumed to be normal; prolonged EEG recordings are a useful means of detecting them31. Functional imaging methods provide additional means for visualizing abnormalities in this hemisphere; epileptogenic foci correspond to areas of hypometabolism on PETz4 or of hypoperfusion on SPECT’. Secondly, uncontrolled seizures from the malformed hemisphere have been said to impair progressively the function of the other hemisphere31, but it is not known when such abnormalities occur. Hemispherectomy might only be necessary just before the functional capacity of the normal hemisphere is to abate as a consequence of contralateral seizures. The present data demonstrate that the functional value of one hemisphere may be preserved after 10 months of subcontinuous contralateral epileptogenic discharges. Frequent discharges have been causally implicated in global mental impairment and lesions with neuronal loss have been reported in epileptogenic foci7. Abnormality may be more extensive since

functional disorders such as hypometabolism and hypoperfusion occur in areas outside the epileptogenie focus’o and bilateral discharge propagation has been reported experimentally after unilateral induced epilepsy**. With serial rCBF studies, the functional value of the non malformed hemisphere can be determined with some accuracy by measuring rCBF over a period of several years and following its maturational pattern. The functional decrease we observed one month after hemispherectomy has also been observed by Chugani6. We show here that such a change is transitory. It may be related to neuronal deafferentation due to the effects of the corpus callosum section as shown by PET in the monkey32. Recovery after hemispherectomy also depends on the brain plasticity of the remaining hemisphere. Recovery seems to be better if hemispherectomy is performed early in life14. Studies by PET and SPECT in normal children demonstrate that maturational cerebral changes persist until at least 10 years of age but are maximal in the first 2 years5s3’. In the limit of time of our study, our data would tend to confirm that hemispherectomy performed in the first year of life may result in a favorable outcome. rCBFfindings

in the cerebellum

Right hyperperfusion disclosed by the first examination may be considered crossed cerebellar activity as observed during contralateral cerebral discharges in partial epilepsy’. Such a phenomenon confirms that the cortico-ponto-cerebellar pathways are functionally mature in the human newborn. Right atrophy observed on the last study illustrates the crossed atrophy of the cerebellum produced by long-standing lesions in a cerebral hemisphere. Our data show that cerebellar atrophy may appear less than one year after cortical resection. A regional cerebral blood flow study by SPECT is, therefore, useful in following cerebral function in unilateral brain malformation before and after hemispherectomy. Preoperatively, such a longitudinal study could help the surgical decision by determining the functional capacity of the hemisphere presumed normal. Postoperatively, it could monitor the global effects of surgery on the

239 remaining cerebral tissue. ACKNOWLEDGEMENTS We thank Dr. Visot, who performed the surgery (Neurochirurgical Department, Hospital Foch, REFERENCES 1 Bonte, F.J., Devous, M.D., Stokely, E.M. and Homan, R.W., Single photon tomographic determination of regional cerebral blood flow in epilepsy, AJNR, 4 (1983) 544-546. 2 Celsis, P., Goldman, T., Henriksen, L. and Lassen N.A., A method for calculating regional cerebral blood flow from emission computed tomography of inert gas concentrations, J. Comput. As&r. Tomogr., 5 (1981) 641-645. 3 Chiron, C., Raynaud, C., Dulac, O., Tzourio, N., TranDinh, S. and Syrota, A., 133-Xe Brain SPECT in a special type of unilateral cerebral malformation. Contribution to prognosis and management, Eur. J. Nucl. Med., 14 (1988) 242. 4 Chiron, C., Raynaud, C., Dulac, O., Tzourio, N., Plouin, P. and Tran-Dinh, S., Study of the cerebral blood flow in partial epilepsy of childhood using the SPECT method, J. Neuroradiol., 16 (1989) 317-324. 5 Chugani, H.T., Phelps, M.E. and Mazziotta, J.C., Positron emission tomography study of human brain functional development , Ann. Neural., 22 (1987) 487-497. 6 Chugani, H.T., Shewmon, D.A., Peacock, W.J., Shields, W.D., Mazziotta, J.C. and Phelps, M.E., Surgical treatment of intractable neonatal-onset seizures: the role of positron emission tomography, Neurology, 38 (1988) 1178-1188. 7 Corsellis, J. and Meldrum, B.S., The pathology of epilepsy. In: W. Blackwood and J. Corsellis (Eds.), Greenfields Neuropathology, Arnold, London, 1976, pp. 771-795. 8 Documentia Geigy, Tables Scientifiques, 6th edn. (1963) 629. 9 Duncan, R., Patterson, J., Bone, I. and Wyper, D.J., Reversible cerebellar diaschisis in focal epilepsy, Lance?,

Suresnes, France), S. Tran-Dinh who performed the MRI, and Mr. Radlo, who revised the manuscript. This work was supported by a grant from C.N.A.M.T.S.-I.N.S.E.R.M. 1988.

Cereb. Blood Flow Metab., 7 Sup. 1(1987) 424. 14 Hoffman, H.J., Hendrick, E.B., Dennis, M. and Armstrong, D., Hemispherectomy for Sturge-Weber syndrome, Child’s Brain, 5 (1979) 233-248. 15 Kalifa, G., Chiron, C., Sellier, N., Demange,

P., Ponsot, G., Lalande, G. and Robain, O., Hemimegalencephaly: MRI imaging in five children, Radiology, 165 (1987)

29-33. 16 Kellersohn, C., Unpublished

data. 17 King, M., Stephenson, J.B.P., Ziervogel, M., Doyle, D. and Galbraith, S., Hemimegalencephaly: a case for hemispherectomy, Neuropediatrie, 16 (1985) 46-55. 18 Lassen, N.A., Assessment of tissue radiation dose in clinical use of radioactive inert gases, with examples of absorbed doses from 3-H, 85-K and 133-Xe, Minerva Nucleare, 8 (1964) 211-217. 19 Lassen, N.A., Henriksen, L. and Paulson, O., Regional ce-

20 21

22

23

12 (1987) 625. 10 Engel, J. Jr., Kuhl, D.E.,

rebral blood flow in stroke by 133-Xenon inhalation and emission tomography, Stroke, 12 (1981) 284-288. Lassen, N.A., Cerebral blood flow tomography with Xenon-133, Semin. Nucl. Med., 15 (1985) 347-356. Lassen, N.A., Cerebral blood flow tomography using Xenon-133 inhalation. Methodological considerations in ‘cerebral blood flow and metabolism measurement’. In: A. Hartman, S. Boyer, Methodological Considerations, Springer-Verlag, Berlin, 1986, pp. 224-233. Makino, K., Tanaka, T. and Yonemasu, Y., Regional cerebral blood flow and kainic acid-induced focal limbic seizures in cats, Epilepsy Rex, 2 (1988) 260-268. Mazoyer, B., Raynaud, C., Tzourio, N., Verrey, B., Chiron, C., Bussy, E., Dulac, O., Lassen, N., Bourguignon, M. and Syrota, A., Error analysis of regional cerebral blood flow (rCBF) measured in children by SPECT with 133-Xe., J. Nucl. Med., 29 (1988) 918. Mazziotta, J.C. and Engel, J., The use and impact of positron computed tomography scanning in epilepsy, Epilep-

Phelps, M.E. and Mazziotta, J.C., Interictal cerebral glucose metabolism in partial epilepsy and its relation to EEG changes, Ann. Neural., 12

24

(1982) 510-517.

25 Powsner,

11 Franck, G., Sadzot, B., Salmon, E., Depresseux, J.C., Grisar, T., Peters, J.M., Guillaume, M., Quaglia, L., Delfiore, G. and Lamotte, D., Regional cerebral blood flow and metabolic rates in human focal epilepsy and status epilepticus, Adv. Neurol., 44 (1986) 935-960. 12 Goddard, B.A. and Ackery, D.M., Xenon-133, Xenon-127 and Xenon-125 for lung function investigations: a dosimetric comparison, J. Nucl. Med., 16 (1975) 780-786. 13 Herscovitch, P., Raichle, M.E. and Goldring, S., Local blood flow increases dramatically in cerebral cortex and subcortical structures during focal seizures in humans, J.

sia, 25 (1984) S86-104.

E.R. and Raeside, D.E., Diagnostic Nuclear Grune and Stratton, New York, 1971, 165-194-201. 26 Raynaud, C., Mazoyer, B., Saucy, J.P., Rancurel, G., Baron, J.C., Samson, Y., Tzourio, N., Bourdoiseau, M., Ricard, S., Bourguignon, M., Lassen, N. and Syrota, A., Regional cerebral blood flow (rCBF) measured by SPECT with 133-Xenon: validation using a PETSPECT comparison, Eur. J. Nucl. Med., 14 (1988) 308. 27 Robain, O., Floquet, C.H., Heldt, N. and Rozenberg, F., Hemimegalencephaly: a clinicopathological study of four cases, Neuropathol. Appl. Neurobiol., 14 (1988) 125-135. Medicine,

240 28 Robain, O., Chiron, C. and Dulac, O., Electron microscopic and Golgi study in a case of hemimegalencephaly, Acta Neuropathol.,

77(1989) 664-666.

29 Theodore,

W.H., Dichirio, G., Margolin, R., Porter, R.J. and Brooks, R.A., Barbiturates depress human cerebral glucose metabolism, Neurology, 36 (1986) 60-64. 30 Tzourio, N., Chiron, C., Raynaud, C., Dulac, O., Mazoyer, B., Bourguignon, M. and Syrota, A., Cerebral maturation during the first 20 months of life studied with the regional cerebral blood flow measurements using SPECT, J. Nucl. Med., 29 (1988) 743.

31 Vigevano, F., Bertini, E., Boldrini, R., Bosman, C., Claps, D., Di Capua, M., Di Rocco, C. and Rossi, J.F., Hemimegalencephaly and intractable epilepsy: benefits of hemispherectomy, Epilepsia, 30 (1989) 833-843. 32 Yamaguchi, T., Kunimoto, M., Pappata, S., Chavoix, C., Riche, D., Chevalier, L., Mazoyer, B., Mazitre, M., Naquet, R. and Baron, J.C., Effects of anterior corpus callosum section on cortical glucose utilization in baboons: a sequential positron emission tomography study, Brain, in press.