Cerebral cortical dysplasia: assessment by MRI and SPECT

Cerebral Cortical Dysplasia: Assessment by MRI and SPECT Kyoko Sasaki, MD,* Yukiko Ohsawa, MD*, Masayuki Sasaki, MD*, Makiko Kaga, MD*, Sachio Takashima, MD*, and Hiroshi Matsuda, MD† The objective of this study was to establish correlations between image findings and pathologic deficits in patients with cerebral cortical malformations. The results of magnetic resonance imaging (MRI) and singlephoton emission computed tomography (SPECT) in addition to clinical data for 15 patients with cerebral cortical malformations were reviewed retrospectively. MRI led to the diagnoses of bilateral perisylvian syndrome, hemimegalencephaly, focal polymicrogyria, band-heterotopia, and focal cortical dysplasia (FCD). Interictal SPECT did not reveal hypoperfusion in any case of polymicrogyria. Ictal SPECT images revealed hyperperfusion of the lesion in three patients with polymicrogyria, with accompanying hyperperfusion of the basal ganglia in two of the three patients. On the other hand, interictal SPECT images demonstrated hypoperfusion of the lesion in four patients with FCD. Ictal SPECT images revealed hypoperfusion of the lesion in two patients, hyperperfusion of the lesion in one patient, and hypoperfusion of the basal ganglia in two patients with FCD. This difference in perfusion between polymicrogyria and FCD observed in this study may reflect histologically different characteristics. This relative hyperperfusion of the cortex and the basal ganglia observed on ictal SPECT, which was found in two polymicrogyria patients with complex partial seizures and partial seizures evolving to secondary generalized seizures, respectively, suggests that the cortical-subcortical interaction is related to the mechanism of loss of consciousness or seizure generation. © 2000 by Elsevier Science Inc. All rights reserved. Sasaki K, Ohsawa Y, Sasaki M, Kaga M, Takashima S, Matsuda H. Cerebral cortical dysplasia: Assessment by MRI and SPECT. Pediatr Neurol 2000;23:410-415.

From Departments of *Child Neurology and †Radiology; National Center Hospital for Mental, Nervous and Muscular Disorders; National Center of Neurology and Psychiatry; Tokyo, Japan.

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Introduction Cerebral cortical malformations are diagnosed by means of neuroimaging and are important as a cause of developmental disorders or epilepsy. The increased sensitivity of magnetic resonance imaging (MRI) in addition to an enhanced awareness of this disorder have resulted in increasing recognition of it [1]. Single-photon emission computed tomography (SPECT) is a noninvasive, functional neuroimaging method for the determination of abnormal areas and assessment of a pathologic state [2]. SPECT has been demonstrated to be helpful in localizing epileptic foci in adults, particularly ictal SPECT, for which sensitivity reaches 97% in temporal lobe epilepsy [3]. However, SPECT studies have been limited in children with cerebral cortical malformations. In this study, we undertook the analysis of clinical records of patients with cerebral cortical malformations in an attempt to correlate imaging findings with pathologic deficits. Patients and Methods The MRIs, SPECT findings, and clinical records of 15 patients with cortical malformations were reviewed retrospectively. The patients ranged in age from 3 months to 36 years at the time of MRI and SPECT. Ten patients were male and five were female. All patients had experienced intractable seizures. Patient charts were reviewed with emphasis on the type of seizures and the results of electroencephalographic studies.

MRI Fifteen patients were scanned at 1.0 T. Axial, coronal, and sagittal spin echo (SE) 450-8000/12-105 (TR/TE) images were obtained with a slice thickness of 5-7 mm, and a 256 ⫻ 256 or 512 ⫻ 512 matrix. These images were evaluated by two pediatric neurologists and a radiologist, respectively. Polymicrogyria comprised a thickened cortex with irregularity of the cortical-white matter junction. The abnormal thickened cortex remained isointense with the normal gray matter [4]. Focal cortical

Communications should be addressed to: Dr. Sasaki, Department of Clinicalpathology; National Center Hospital for Mental, Nervous and Muscular Disorders; National Center of Neurology and Psychiatry; 4-1-1, Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan. Received December 9, 1999; accepted August 22, 2000.

© 2000 by Elsevier Science Inc. All rights reserved. PII S0887-8994(00)00223-X ● 0887-8994/00/$—see front matter

Table 1.

MR and SPECT findings

Patient

Age/sex

MR findings

Seizure type

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

4 yr/M 12 yr/F 29 yr/M 8 yr/F 11 mo/M 36 yr/M 25 yr/M 17 yr/M 5 yr/F 35 yr/F 3 mo/M 5 yr/M 18 yr/F 18 yr/M 27 yr/M

Lt. hemimegalencephaly Bil. perisylvian polymicrogyria Bil. perisylvian polymicrogyria Lt. FPL polymicrogyria Rt. FL to insula polymicrogyria Rt. FL polymicrogyria Rt. FL polymicrogyria Rt. FL polymicrogyria Rt. FL polymicrogyria Bil. FL band-heterotopia Lt. operculum to FL FCD Lt. FL FCD Lt. TL FCD Rt. FL FCD Rt. PL FCD

CPS TS CPS TS PSG CPS SPS TS PSG CPS CPS TS GTCS SPS SPS

Abbreviations: BG ⫽ Basal ganglia Bil. ⫽ Bilateral CPS ⫽ Complex partial seizures F ⫽ Female FCD ⫽ Focal cortical dysplasia FL ⫽ Frontal lobe FPL ⫽ Frontal and parietal lobes GTCS ⫽ Generalized tonic clonic seizures 1 ⫽ Hyperperfusion 2 ⫽ Hypoperfusion Lt ⫽ Left

M mo 3 PSG Rt. SPS SL TL TS yr

⫽ ⫽ ⫽ ⫽ ⫽ ⫽ ⫽ ⫽ ⫽ ⫽

Interictal SPECT Lesion SL BG 1 1 3 3 1 3 1 3 1 2

3 3 3 3 3 2 3 3 3 1

3 1 3 3 3 3 1 2 3 2

2 2 2

2 3 3

2 3 3

Lesion

Ictal SPECT SL

BG

1 1

3 3

1 3

1

1

1

2 2

1 3

2 2

1

3

3

Male Months old Normoperfusion Partial seizures evolving to secondary generalized seizures Right Simple partial seizures Surrounding lesion Temporal lobe Tonic Seizure Years old

dysplasia comprised cortical thickening with irregular, bumpy inner and outer cortical surfaces, broad gyri, and shallow sulci. The gray-white junction was indistinct [1,5]. The signals of the cortex and white matter were abnormal. The signal of the cortex was increased slightly in T1-weighted images, whereas the signal of the subcortical white matter was decreased in T1- and increased in T2-weighted images [5].

SPECT The regional cerebral blood flow distribution was evaluated by means of an intravenous injection of N-isopropyl-[123I] p-iodoamphetamine (123I-IMP), 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO), or 99mTc-ethyl cysteinate dimer (99mTc-ECD). They were injected interictally at least 3 hours after the last seizure. For ictal SPECT, they were injected during convulsions lasting for more than 15 seconds. The regional cerebral blood flow (rCBF) distribution was divided into the three degrees of hyperperfusion, normoperfusion, and hypoperfusion. Increased rCBF or decreased rCBF was determined in comparison with rCBF in morphologically normal regions, as assessed by MRI.

Ictal SPECT images were obtained in three patients with polymicrogyria, which indicated hyperperfusion of the lesion in all three patients with accompanying hyperperfusion of the basal ganglia in two of the three patients (Figs 1B, 2B, and 3C). SPECT revealed hyperperfusion of the lesion interictally in four patients and normoperfusion interictally in four patients of nine patients with polymicrogyria but did not reveal hypoperfusion in any case of polymicrogyria (Fig 3B). On the other hand, interictal SPECT images were obtained in four patients with FCD. They depicted hypoperfusion of the lesion in all four patients. Ictal SPECT images were obtained in three patients with FCD, which demonstrated hypoperfusion of the lesion in two patients, hyperperfusion of the lesion in one patient, and hypoperfusion of the basal ganglia in two patients (Fig 4B).

Results

Discussion

The MRI findings (Table 1) led to the diagnoses, which comprised hemimegalencephaly (Patient 1) (Fig 1A), bilateral perisylvian syndrome (Patients 2 and 3) (Fig 2A), focal polymicrogyria (Patients 4-9) (Fig 3A), band-heterotopia (Patient 10), and focal cortical dysplasia (FCD) (patients 11-15) (Fig 4A). The lesions were excised, and the diagnoses were confirmed histologically in three patients with polymicrogyria and FCD (Patients 4, 11, and 12).

Polymicrogyria of the cerebral cortex is a developmental abnormality characterized by excessive surface convolution. Two major histologic varieties of polymicrogyria are recognized: a four-layered type and an unlayered type. The basic cytoarchitectonic lesion in polymicrogyria is midcortical ischemic laminar necrosis predominating in layer 5 [6,7]. This cortical laminar necrosis enhances the developmental growth difference between the inner and outer cortical layers [6,8]. This mechanism seems to be the

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Figure 1. Left hemimegalencephaly (Patient 1). (a) Inversion-recovery MRI (TR: 7000 ms; TE: 60 ms; axial section) revealing a polymicrogyric lesion in the left hemisphere. A gray matter intensity lesion can also be seen in the left subcortical and deep white matter. (b) 99mTc-ECD ictal SPECT. Note the hyperperfusion over the left polymicrogyric lesion and the left thalamus.

origin of the polymicrogyric cortical overfolding, which occurs between 16 and 28 fetal weeks after neuronal migration [7]. The leptomeninges covering the polymicro-

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Figure 2. Bilateral perisylvian polymicrogyria (patient 2). (a) T1weighted MRI (TR: 570 ms; TE: 12 ms; axial section). (b) 99mTc-ECD ictal SPECT. Note the hyperperfusion over the surrounding bilateral sylvian fissures.

Figure 3. Focal polymicrogyria (patient 5). (a) T1-weighted MRI (TR: 500 ms; TE: 12 ms; axial section) demonstrating a polymicrogyric lesion in the right frontal area to the insula. (b) 99mTc-HMPAO interictal SPECT demonstrating hyperperfusion in the right polymicrogyric lesion. (c) 99mTc-HMPAO ictal SPECT. Note the hyperperfusion in the right polymicrogyric lesion, the bilateral thalami (arrows), and the brainstem (arrowhead).

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Figure 4. (a) Focal cortical dysplasia (patient 11). T1-weighted MRI (TR: 500 ms; TE: 12 ms; axial section) demonstrating brain shrinkage, and cortical thickening and irregular gyri in the left operculum to the frontal area. (b) 99mTc-ECD ictal SPECT revealing hypoperfusion in the lesion and hyperperfusion in the adjacent frontal area.

gyric cortex can be abnormally vascularized because of persistent fetal leptomeningeal vascularization. Anomalous venous drainage is common in areas of polymicrogyria [9]. Focal cortical dysplasia is one of the focal malformations of cortical development with the presence of dysplastic cells. Dysplastic cells include cytomegalic neurons,

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oval neurons, ballooned cells, bizarre neurons, and bizarre glial cells [10]. They are distributed in a panlaminar manner, with involvement of the superficial cortex, and are extended along a diffuse front into the subcortical white matter, which results in a gray-white junction whose margins are typically blurred. These cells are immunoreactive for glial fibrillary acidic protein and synaptophysin,

markers of astrocytic and neuronal origins, respectively [5]. The pathogenesis of FCD remains unknown, but the immunoreactivity of the dysplastic cells suggests that FCD results from a failure of pluripotential cells (matrix cells) to decide on a single lineage [11]. Polymicrogyria is a cytoarchitectonic abnormality with aberrant vascularization, but FCD comprises dysplasticity and immaturity of neuronal cells and also abnormal polarization of neuronal cells. In this SPECT study, interictal SPECT revealed hyperperfusion or normoperfusion in the lesions of polymicrogyria cases, but hypoperfusion in FCD cases. This difference in perfusion between polymicrogyria and FCD observed in this study may reflect histologically different characteristics. The second finding was the hypoperfusion in a lesion but hyperperfusion or normoperfusion in its surrounding lesions in some FCD patients on ictal SPECT, which may indicate that the lesion of FCD is not epileptogenic focus. The third finding was the hyperperfusion in a lesion and its surrounding area, as well as the basal ganglia, including the thalamus on ictal SPECT. This relative hyperperfusion of the cortex and the basal ganglia observed on ictal SPECT was found in two polymicrogyria patients with complex partial seizures and partial seizures evolving to secondary generalized seizures, respectively. Chugani et al. have reported a positron emission tomography (PET) study in an attempt to identify the neuroanatomic substrates that mediate seizures of infantile spasms. The most consistent abnormality on PET, seen in 32 infants, is a symmetric hypermetabolism in the lenticular nuclei, and in approximately half of the cases, the brainstem appears more prominent compared to normal infants. From these findings, the authors propose that the raphe-striatal serotonergic pathway and raphe-cortical projections play important roles in the pathogenesis of infantile spasms [12]. The hyperperfusion in a lesion and its surrounding area, as well as the basal ganglia, including the thalamus observed on ictal SPECT in this study appears to support these hypotheses, and the cortical-subcortical interaction on the

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