Faculty Bibliography

OBJECTIVE:To determine whether the major temporal lobe white matter tracts in patients with temporal lobe epilepsy manifest abnormal water diffusion properties. METHODS:Diffusion tensor MRI measurements were obtained from tractography for uncinate, arcuate, inferior longitudinal fasciculi and corticospinal tract in 13 children with left temporal lobe epilepsy and normal conventional MRI, and the data were compared to measurements in 12 age-matched normal volunteers. The relationship between tensor parameters and duration of epilepsy was also determined. RESULTS:All four tracts in the affected left hemisphere showed lower mean anisotropy, planar and linear indices, but higher spherical index in patients versus controls. Diffusion changes in the left uncinate and arcuate fasciculus correlated significantly with duration of epilepsy. Arcuate fasciculus showed a reversal of the normal left-right asymmetry. Various diffusion abnormalities were also seen in the four tracts studied in the right hemisphere. CONCLUSION/CONCLUSIONS:Our findings indicate abnormal water diffusion in temporal lobe and extra-temporal lobe tracts with robust changes in the direction perpendicular to the axons. Diffusion abnormalities associated with duration of epilepsy suggest progressive changes in ipsilateral uncinate and arcuate fasciculus due to chronic seizure activity. Finally, our results in arcuate fasciculus are consistent with language reorganization to the contralateral right hemisphere.

OBJECT/OBJECTIVE:Fever is a common occurrence after cerebral hemispherectomy in children and prolongs the hospital stay. The authors determined whether an external ventriculostomy might reduce the incidence of fever following a hemispherectomy. METHODS:The postoperative courses of 27 patients who had undergone cerebral hemispherectomy for intractable seizures were retrospectively analyzed. RESULTS:Thirteen children underwent an external ventriculostomy, and only 1 had an elevated axillary body temperature of > or = 39 degrees C during the postoperative period. Among 14 patients who did not undergo an external ventriculostomy, 7 had a posthemispherectomy fever of > or = 39 degrees C. Patients who underwent an external ventriculostomy had a lower risk of postoperative fever compared with those who did not undergo the procedure (8 vs 50%, respectively; p = 0.03, Fisher exact test). None of the patients had an infection accounting for the cause of the fever. The hospital stay for patients who had undergone postoperative external ventriculostomy was significantly shorter than for those who had not (7.2 +/- 2 vs 11.3 +/- 5 days, respectively; p = 0.01, Student t-test). CONCLUSIONS:The use of external ventriculostomy following hemispherectomy for intractable epilepsy in children reduces the incidence of postoperative fever due to infection.

This article discusses and reviews the role and contribution of PET in understanding the structural and functional changes that occur during brain development, and how these changes relate to behavioral and cognitive development in the infant and child. Data regarding various aspects of brain development, such as glucose metabolism, protein synthesis, and maturation and development of neurotransmitter systems will help in understanding the pathogenesis and neurologic basis of various developmental and neurologic disorders. This may help in following disease evolution and progression, planning and development of various therapeutic interventions, timing these interventions and monitoring their responses, and rendering long-term prognostication.

Several studies have shown that seizure-induced cellular and molecular changes associated with chronic epilepsy can lead to functional and structural alterations in the brain. Chronic epilepsy, when medically refractory, may be associated with an expansion of the epileptic circuitry to involve complex interactions between cortical and subcortical neuroanatomical substrates. Progress in neuroimaging has led not only to successful identification of epileptic foci for surgical resection, but also to an improved understanding of the functional and microstructural changes in long-standing epilepsy. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) are all promising tools that can assist in elucidating the underlying pathophysiology in chronic epilepsy. Studies using PET scanning have demonstrated dynamic changes associated with the evolution from acute to chronic intractable epilepsy. Among these changes are data to support the existence of secondary epileptogenesis in humans. MRI with DTI is a powerful tool which has the ability to characterize microstructural abnormalities in epileptic foci, and to demonstrate the white matter fibers and tracts participating in the epileptic network. In this review, we illustrate how PET and DTI can be applied to depict the functional and microstructural alterations associated with chronic epilepsy.

The mechanism of altered glucose metabolism seen on positron emission tomography (PET) in focal epilepsy is not fully understood. We determined the association between interictal glucose metabolism and interictal neuronal activity, using PET and electrocorticography (ECoG) measures derived from 865 intracranial electrode sites in 11 children with focal epilepsy associated with tuberous sclerosis complex (TSC) (age: 0.5-16 years) undergoing epilepsy surgery. A multiple linear regression analysis was applied to each patient, to determine whether the glucose uptake at each electrode site on interictal PET was predicted by ECoG amplitude powers and interictal spike-frequency measured in the given electrode site. The regression slopes as well as R-square values (an indicator of fitness of the regression models) were finally averaged across the 11 patients. The mean regression slope for delta amplitude power was -0.0025 (95% CI: -0.0045 to -0.0004; P = 0.02 based on one-sample t-test) and that for spike frequency was -0.023 (95% CI: -0.042 to -0.0038; P = 0.02). On the other hand, the mean regression slopes for the remaining ECoG amplitude powers (theta, alpha, sigma, beta, and gamma activities) were not significantly different from zero. The mean R-square value was 0.39. These results suggest that increased delta-slowing and frequent spike activity were independently and additively associated with glucose hypometabolism in children with focal epilepsy associated with TSC. Association between frequent interictal spike activity and low glucose metabolism may be attributed to slow-wave components following spike discharges on ECoG recording, and a substantial proportion of the variance in regional glucose metabolism on PET could be explained by electrophysiological traits derived from conventional subdural ECoG recording.

A 7-year-old girl presented with a cluster of seizures occurring in one day and followed by the development of paranoid delusions. Her electroencephalogram (EEG) revealed a psychomotor variant. Cranial MRI was normal, but the 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) positron emission tomography (PET) scan showed hypometabolism in the left inferior frontal cortex. Her psychotic symptoms occurred episodically. Three years later, she developed hypermotor seizures associated with a fearful look. Video/EEG monitoring captured seizures of left frontotemporal onset. Her seizures became drug resistant and she underwent epilepsy surgery. Intracranial electrocorticography captured spontaneous and electrically induced seizures with onset in the left inferior frontal region, which was resected. She became seizure-free and her psychosis resolved. This case illustrates that frontal lobe epilepsy can present solely with psychotic symptoms, which may delay the diagnosis of epilepsy. We suggest that these cases may be underdiagnosed. When epilepsy is suspected and if MRI fails to demonstrate an abnormality, FDG PET scanning and video/EEG monitoring should be considered.

Reorganization involving residual visual pathways with unilateral damage to the primary visual cortex was previously described. Using diffusion tensor imaging, we measured water diffusion-related changes in the optic radiation contralateral to occipital lobe ablation in children with intractable epilepsy. We studied 10 children who had undergone a resection of the unilateral occipital cortex and 13 control subjects. Diffusion tensor imaging was acquired using a 1.5 Tesla magnetic resonance scanner. Fiber bundles representing optic radiation were tracked. Diffusion parameters included mean fractional anisotropy, apparent diffusion coefficient, and diffusion parallel and perpendicular to the fiber tract. In the surgical group, fractional anisotropy values of optic radiation contralateral to the side of resection exhibited a significant positive partial correlation (r = 0.752, P = 0.019) with duration of time between surgery and diffusion tensor imaging acquisition, after controlling for age. The apparent diffusion coefficient and parallel diffusivity were higher in the surgical versus the control group, but did not differ among patients. After unilateral resection of the occipital lobe, the contralateral optic radiation undergoes significant changes in anisotropy. Such structural white-matter changes may represent an adaptive response because of unilateral occipital ablation, and may account for plasticity changes observed in functional magnetic resonance imaging.

BACKGROUND AND PURPOSE/OBJECTIVE:Serotonin is a major regulator of structural brain plasticity, which may occur following cortical resection in humans. In this study we used positron emission tomography (PET) with alpha[11C]methyl-l-tryptophan (AMT) to evaluate serotonergic alterations in subcortical structures following cortical resection in children with intractable epilepsy. METHODS:AMT uptake in the thalamus and lentiform nucleus was evaluated postoperatively (1-89 months following resection) in 19 children (mean age: 8.7 years) with a previous cortical resection due to intractable epilepsy. Ten children with partial epilepsy but without resection and seven normal children served as controls. RESULTS:There was an increased AMT uptake in the lentiform nucleus ipsilateral to the resection as compared to the contralateral side (mean asymmetry: 4.2+/-3.0%), and the asymmetries were significantly higher than those measured in the control groups (p<or=0.001). Post-resection asymmetry indices in the lentiform nucleus correlated inversely with postoperative time (r=-0.67; p=0.002), but not with age (p=0.29) or the extent of resection (p=0.77). In contrast, thalamic AMT uptake asymmetries were not different among the three groups (p=0.63). CONCLUSIONS:Cortical resection results in a sustained increase of AMT uptake in the lentiform nucleus, suggesting increased serotonin synthesis. Serotonergic activation in the deafferented striatum may play a role in the functional reorganization of cortico-striatal projections in humans.

OBJECTIVE:To investigate cortical association tracts using diffusion tensor imaging (DTI) in children with global developmental delay of unknown etiology. STUDY DESIGN/METHODS:We performed DTI in 20 patients (age range: 18-83 months, mean: 45 +/- 16 months, 12 males) with a history of global developmental delay and 10 typically developing children (age range: 26-99 months, mean: 54 +/- 24 months, 5 males). DTI tractography was performed to isolate major cortical association tracts. RESULTS:In 9 out of 20 patients, arcuate fasciculus (AF) was absent bilaterally and in another 2 patients, it was absent in left hemisphere. In contrast, AF was present bilaterally in all typically developing children. Fractional Anisotropy (FA) of inferior longitudinal fasciculus (ILF) was asymmetric in the control group but not in the developmental delay group (P = .04). FA was significantly reduced in right ILF in developmentally delayed children compared with controls (P = .03). FA of other association tracts was not different between patients and controls (P = NS). The apparent diffusion coefficient (ADC) showed no asymmetry for these tracts in controls or developmentally delayed children (P = NS). CONCLUSIONS:DTI can be used to identify absence of AF and inadequate maturation of ILF in children with global developmental delay of unknown etiology.

OBJECTIVE:To utilize diffusion tensor tractography and evaluate the integrity of the corticospinal tract in children with unilateral Sturge-Weber syndrome (SWS). METHODS:Sixteen children (age: 1.5-12.3 years) with SWS involving one hemisphere and varying degrees of motor deficit, underwent magnetic resonance imaging (MRI) as part of a prospective clinical research study. Diffusion tensor imaging (DTI) was obtained and fiber tracking of the corticospinal tract was performed yielding average FA and ADC values along the pathway. These values were compared between the two hemispheres (affected vs. unaffected) and also correlated with the degree of motor deficits, after correction for age. RESULTS:Corticospinal tract FA values on the side of the affected hemisphere were lower (p=0.008) and ADC values were higher (p=0.011) compared to the normal side. Furthermore, FA and ADC values on the side of the angioma did not show the normal age-related variations, which the contralateral corticospinal pathway values did demonstrate. Although none of the patients had severe hemiparesis, those with moderate motor deficit had increased ADC values, as compared to those with mild (p=0.009) or no motor deficit (p=0.045). CONCLUSION/CONCLUSIONS:MRI with DTI shows abnormalities of the corticospinal tract in children with SWS even before severe motor impairment develops. Thus, DTI can be a clinically useful method to evaluate the integrity of the corticospinal tract in young children who are at risk for progressive motor dysfunction.