Faculty Bibliography

Postnatal deprivation is associated with neurocognitive delay/dysfunction. Although "catch up" in global cognition following adoption has been reported, this study examined the incidence of specific absolute impairment in adopted children with intact global cognitive functioning. Eighty-five children (38 males, mean age = 112.8, SD = 30.3 months; range 61-209 months) raised from birth in orphanages underwent comprehensive neuropsychological evaluation. Fifty-four were deemed globally intact (IQ > 85). Of those deemed globally intact, 46% evidenced absolute impairment in at least one domain of functioning. Duration of stay in the orphanage was directly associated with incidence of impairment and number of domains affected. A substantial proportion of participants evidenced persistent, absolute impairment in one or more domains of neurocognitive function despite integrity of basic intellectual functions.

Preliminary studies suggest that alpha[(11)C]methyl-l-tryptophan positron emission tomography can detect the epileptic focus within malformations of cortical development. We determined the sensitivity and specificity of alpha-[(11)C]methyl-l-tryptophan positron emission tomography in identifying epileptic focus in children with intractable, neocortical epilepsy with and without malformations of cortical development. Seventy-three epileptic children were classified into lesional and nonlesional groups, and compared regarding focal increased alpha-[(11)C]methyl-l-tryptophan uptake. The sensitivity and specificity of focal increased alpha-[(11)C]methyl-l-tryptophan uptake, using intracranial electroencephalogram localization of seizure onset as the standard, were compared between lesional and nonlesional groups. The specificity of alpha-[(11)C]methyl-l-tryptophan positron emission tomography for detecting seizure onset lobe was equally high in lesional (97%) and nonlesional groups (100%), whereas sensitivity was higher in the lesional than the nonlesional group (47% versus 29%; P = 0.047). The incidence of alpha-[(11)C]methyl-l-tryptophan uptake abnormality was higher in the lesional than the nonlesional group (P < 0.01). Alpha-[(11)C]methyl-l-tryptophan positron emission tomography localized and visualized epileptogenic regions in 25% of patients with nonlocalizing magnetic resonance imaging. Although overall sensitivity of alpha-[(11)C]methyl-l-tryptophan positron emission tomography in identifying neocortical epileptic focus is modest, specificity is extremely high. When an alpha-[(11)C]methyl-l-tryptophan focus is detected, it likely represents the epileptogenic region to be resected.

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.

PURPOSE/OBJECTIVE:To evaluate the efficacy of susceptibility weighted imaging (SWI) in comparison to standard T1 weighted postgadolinium contrast (T1-Gd) MRI in patients with Sturge-Weber Syndrome (SWS). MATERIALS AND METHODS/METHODS:Twelve children (mean age, 5.6 years) with the diagnosis of SWS and unilateral hemispheric involvement were recruited prospectively and examined with high resolution three dimensional SWI and conventional T1-Gd. Both SWI and T1-Gd images were evaluated using a four-grade scoring system according to six types of imaging findings (enlargement of transmedullary veins, periventricular veins, and choroid plexus, as well as leptomeningeal abnormality, cortical gyriform abnormality, and gray matter/white matter junctional abnormality). The scores of SWI versus T1-Gd images were then compared for each type of abnormality. RESULTS:SWI was superior to T1-Gd in identifying the enlarged transmedullary veins (P = 0.0020), abnormal periventricular veins (P = 0.0078), cortical gyriform abnormalities (P = 0.0020), and gray matter/white matter junction abnormalities (P = 0.0078). Conversely, T1-Gd was better than SWI in identifying enlarged choroid plexus (P = 0.0050) and leptomeningeal abnormalities (P = 0.0050). CONCLUSION/CONCLUSIONS:SWI can provide useful and unique information complementary to conventional contrast enhanced T1 weighted MRI for characterizing SWS. Therefore, SWI should be integrated into routine clinical MRI protocols for suspected SWS.

We determined if high-frequency gamma-oscillations (50- to 150-Hz) were induced by simple auditory communication over the language network areas in children with focal epilepsy. Four children (aged 7, 9, 10 and 16 years) with intractable left-hemispheric focal epilepsy underwent extraoperative electrocorticography (ECoG) as well as language mapping using neurostimulation and auditory-language-induced gamma-oscillations on ECoG. The audible communication was recorded concurrently and integrated with ECoG recording to allow for accurate time lock on ECoG analysis. In three children, who successfully completed the auditory-language task, high-frequency gamma-augmentation sequentially involved: i) the posterior superior temporal gyrus when listening to the question, ii) the posterior lateral temporal region and the posterior frontal region in the time interval between question completion and the patient's vocalization, and iii) the pre- and post-central gyri immediately preceding and during the patient's vocalization. The youngest child, with attention deficits, failed to cooperate during the auditory-language task, and high-frequency gamma-augmentation was noted only in the posterior superior temporal gyrus when audible questions were given. The size of language areas suggested by statistically significant high-frequency gamma-augmentation was larger than that defined by neurostimulation. The present method can provide in vivo imaging of electrophysiological activities over the language network areas during language processes. Further studies are warranted to determine whether recording of language-induced gamma-oscillations can supplement language mapping using neurostimulation in presurgical evaluation of children with focal epilepsy.

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.

BACKGROUND:In Sturge-Weber syndrome (SWS), structural MRI abnormalities are most common in the posterior brain regions. Frontal lobe involvement increases the risk of motor impairment. The goal of this study was to determine whether Magnetic Resonance Spectroscopic Imaging (MRSI) can improve detection of frontal lobe involvement in children with SWS. METHODS:Sixteen children (age: .9-10.4 years) with unilateral SWS underwent MRI with MRSI prospectively. N-acetyl-aspartate (NAA) and choline asymmetries in the posterior and frontal regions were measured. RESULTS:Eight children presented normal-appearing frontal lobes on conventional MRI, but 7 of them showed abnormal NAA and/or choline content in the frontal lobe of the affected hemisphere. Lower frontal lobe gray matter NAA was associated with earlier onset of seizures (r= .76; P= .04) and impaired motor function (r=-.89, P < .001). Frontal NAA asymmetry was an independent predictor of motor function in a regression analysis (P= .01) CONCLUSION/CONCLUSIONS:MRSI is more sensitive than conventional structural MRI for detection of frontal lobe involvement in SWS. Decreased frontal lobe NAA is an excellent predictor of motor functions. Thus, MRSI can provide complementary information for the assessment of normal-appearing brain regions, and may assist prognosis evaluation in children with SWS.

Recent studies have suggested that cortical gamma-oscillations are tightly linked with various forms of physiological activity. In the present study, the dynamic changes of intracranially recorded median-nerve somatosensory-evoked potentials (SEPs) and somatosensory-induced gamma-oscillations were animated on a three-dimensional MR image, and the temporal and spatial characteristics of these activities were analysed in 10 children being evaluated for epilepsy surgery. Visual and quantitative assessments revealed that short-latency SEPs and somatosensory-induced gamma-oscillations predominantly involved the post-central gyrus and less intensely involved the pre-central gyrus and the anterior parietal lobule. Formation of a dipole of N20 peak with opposite polarities across the central sulcus was well delineated in animation movies. High-frequency (100-250 Hz) somatosensory-induced gamma-oscillations emerged in the post-central gyrus at 13.6-17.5 ms after median-nerve stimulation, gradually slowed down in frequency around and below 100 Hz, and progressively involved the neighbouring areas. A substantial proportion of somatosensory-induced gamma-oscillations was initially phase-locked and the proportion of a non-phase-locked component gradually increased over time. The primary motor hand areas proven by cortical stimulation frequently coincided with the sites showing the largest N20 peak and the largest somatosensory-induced gamma oscillations. In vivo animation of SEPs and somatosensory-induced gamma oscillations both may be utilized to localize the primary sensory-motor hand area in pre-surgical evaluation. The dipole on SEPs is consistent with the previously accepted notion that the cortices along the central sulcus are activated. The high-frequency somatosensory-induced gamma-oscillations in the post-central gyrus may represent the initial neural processing for external somatosensory stimuli, whereas the subsequent lower-frequency oscillations might represent the reafferent cortical activity occurring in larger cortical networks.

The positron emission tomography radiotracer (11)C-PK11195 selectively binds to the peripheral-type benzodiazepine receptors expressed in activated microglia and can, therefore, detect areas of neuroinflammation. (11)C-PK11195 positron emission tomography was used in determining the surgical treatment of a 5-year-old boy with intractable epilepsy due to encephalitis of unknown etiology. After 4 months of treatment in the pediatric intensive care unit for altered consciousness and refractory seizures despite multiple anticonvulsants, including continuous midazolam infusion, (11)C-PK11195 positron emission tomography revealed an area of increased uptake in the left temporal-occipital cortex. Because the majority of his seizures at this stage of his illness emanated from the same region, the patient underwent left temporal-occipital cortical resection guided by intraoperative electrocorticography. The surgery resulted in significant recovery, and he could be discharged from the hospital. Focal areas of neuroinflammation may play an important role in seizure pathogenesis in a subset of patients with refractory seizures associated with encephalitis. In such cases, (11)C-PK11195 positron emission tomography may highlight the region of maximal inflammation for palliative surgical treatment.

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.