Faculty Bibliography

We report a four-year-old boy with Landau-Kleffner Syndrome (LKS) characterized by episodic receptive aphasia lasting for few weeks followed by gradual recovery of baseline language functions. Neuropsychological evaluation during an episode showed severe impairment in verbal skills and comprehension, but relative preservation of non-verbal skills. Although he could carry on a conversation during remission, neuropsychological evaluation demonstrated findings reflective of receptive language deficits. Prolonged EEG disclosed frequent sharp-wave activity in the left and right temporal regions but no electrographic seizures. Glucose metabolism PET scan during the fourth episode of aphasia revealed intense hypermetabolism in the left temporal neocortex. Awake EEG during the PET tracer uptake period showed 6.0 spikes/min in the left temporal region and 4.0 spikes/min in the right. A repeat PET scan during remission showed hypometabolism in the left temporal cortex. Awake EEG during the FDG uptake period showed 16.0 spikes/min in the right temporal region and 0.3 spikes/min in the left. During his fifth aphasic episode, EEG (without PET) showed 0.16 spikes/min in the right temporal region and none in the left. Intermittent short episodes of predominantly receptive aphasia with near-total recovery between episodes can be one of the clinical presentations of LKS. This case illustrates the dynamic changes of glucose metabolism in the temporal lobe during episodes of aphasia and remission in a case with LKS. The clinical course of our patient with transient EEG and PET findings suggest that glucose metabolism in LKS cannot be attributed solely to interictal epileptiform activities on scalp EEG.

We assessed the structural and functional imaging features of cerebellar lesions and their neurobehavioral correlates in a large cohort of patients with tuberous sclerosis complex. A consecutive series of 78 patients with tuberous sclerosis complex underwent magnetic resonance imaging (MRI) and positron emission tomography (PET) studies with [(18)F]fluorodeoxyglucose (FDG) and alpha-[(11)C]methyl-l-tryptophan (AMT) as part of their evaluation for epilepsy surgery. Neurobehavioral assessment included the Gilliam Autism Rating Scales (GARS) and the Vineland Adaptive Behavior Scales (VABS). Twenty-one patients (27%) had cerebellar lesions (10 boys; mean age 9 +/- 8 years; 9 had right-sided, 10 had left-sided, and 2 had bilateral cerebellar lesions). The lesions showed decreased glucose metabolism (0.79 +/- 0.10) and increased (1.04 +/- 0.10) AMT uptake compared with the normal (nonlesional) cerebellar cortex. Comparisons between patients with (n = 20) and without (n = 57) a cerebellar lesion on neurobehavioral functioning, controlling for the number and location of cortical tubers, revealed that the cerebellar lesion group had higher overall autistic symptomatology. Within-group analyses of the cerebellar lesion group revealed that children with right-sided cerebellar lesions had higher social isolation and communicative and developmental disturbance compared with children with left-sided cerebellar lesions. The side of the cerebellar lesion was not related to adaptive behavior functioning. These findings provide additional empiric support for a role of the cerebellum in autistic symptomatology. Further investigation of the potential role of the right cerebellum in autism, particularly with regard to the dentatothalamofrontal circuit, is warranted.

OBJECT/OBJECTIVE:Preservation of the vein of Labbé is recommended to prevent temporal lobe infarction after skull base surgery. However, the importance of preserving the vein in epilepsy surgery involving resection of the temporal lobe is unclear. METHODS:Retrospective analysis was performed in 47 cases, in which patients underwent temporal lobe resection, out of 148 cases in which patients underwent surgery for intractable seizures over a 5-year period. Standard temporal lobe resection anterior to the vein of Labbé was performed in 11 patients. In 24 patients, the temporal lobe resection extended posterior to the vein of Labbé; the vein was preserved in eight patients, who underwent surgery prior to 2002, and resected in the other 16 patients, who underwent surgery after 2002. Twelve patients underwent a temporoparietooccipital resection. There was no significant difference in the pattern of venous anatomy (based on analysis of the relative size of veins [chi-square test, p = 0.1] and the number of superficial veins draining the temporal lobe [p = 1]) in patients in whom the vein was resected compared with those in whom it was preserved. No patient experienced postoperative infarction. CONCLUSIONS:The authors conclude that the vein of Labbé may be safely resected in epilepsy surgery involving temporal lobe resection. The decision whether to resect the vein need not be based on the surface venous drainage pattern or number of veins draining the temporal lobe.

UNLABELLED:FUNCTIONAL NEUROIMAGING: Although the primary imaging modality in the management of epilepsy is magnetic resonance imaging MRI, functional neuroimaging with positron-emission tomography (PET) and single photon emission computed tomography (SPECT) often provides complementary information and, in a number of situations, provides unique information that cannot be obtained with MRI. The most commonly used PET tracers used for epilepsy evaluation are 2-deoxy-2-[(18)F]fluoro-D: -glucose (FDG) and [(11)C]flumazenil (FMZ). Recently, interictal PET with alpha-[(11)C]methyl-L: -tryptophan was found to be highly specific for the epileptic focus and can differentiate between epileptogenic and nonepileptogenic lesions in the same patient (e.g., in patients with tuberous sclerosis). DISCUSSION/CONCLUSIONS:In this review, we discuss clinical applications of these three PET tracers in drug-resistant temporal and extratemporal lobe epilepsy, selected epilepsy syndromes of childhood, lesional and nonlesional epilepsy, and the challenges of imaging secondary epileptic foci. A brief discussion of SPECT applications in epilepsy is also included. With further development of new tracers highly sensitive and specific for epileptogenic brain regions, the presurgical evaluation of refractory epilepsy will be greatly facilitated. Approximately 0.5 to 1.0% of the population suffer from epilepsy, of which 15-20% are intractable. Infants and children, whose seizures have a focal onset are refractory to anticonvulsants and are prolonged, tend to have the worst cognitive outcome [Meador KJ, Neurology 58 (Suppl 5):S21-S26, 2002]. Seizures themselves affect the developing brain and contribute to an adverse neurologic outcome (Holmes, Pediatric Neurology 33:1-110, 2005). CONCLUSION/CONCLUSIONS:Therefore, in treating children with intractable epilepsy, it is important to consider seizure control and to give allowance for normal cognitive development.

Congenital perisylvian syndromes are late migration/cortical organization disorders associated with distinctive clinical and imaging features. The clinical, magnetic resonance imaging, and 2-deoxy-2-[18F] fluoro-D-glucose (FDG) positron emission tomography scan findings of six children (age range: 3.2-16.7 years; 5 males) with congenital perisylvian syndrome were evaluated. The patients presented with heterogenous neurologic impairments, depending upon the involved hemisphere and the extension of perisylvian malformation. Two manifested bilateral malformation and four manifested unilateral. The characteristic MRI finding consisting of a vertically oriented sylvian fissure continuous with the central and postcentral sulcus was associated with variable extension of bordering polymicrogyric cortex. The positron emission tomography scans of all patients revealed perisylvian metabolic abnormalities corresponding to the magnetic resonance imaging-defined abnormality. Variable extent of abnormal glucose metabolism was also observed in areas with normal magnetic resonance imaging features. All patients with unilateral magnetic resonance imaging abnormality exhibited abnormal glucose metabolism also in the contralateral side. The two patients with bilateral malformation had more extensive positron emission tomography abnormalities than the morphologic anomalies on MRI. Although MRI remains the diagnostic gold standard to detect the lesion, positron emission tomography scan is helpful to evaluate the full functional extension of the cortical anomaly, thereby contributing to the definition of the clinical severity of the syndrome.

Following cerebral hemispherectomy, the corticospinal tract is believed to undergo reorganizational changes, which can induce enhanced function of the contralateral motor pathway and mediate partial recovery of motor function. The aim of this study was to use diffusion tensor imaging to investigate the effects of hemispherectomy on the corticospinal tract, with particular attention to the corticospinal tract contralateral to the resection. Diffusion tensor imaging would presumably detect microstructural abnormalities through quantitative measurements of the fiber tract integrity and orientation. Four patients with anatomic hemispherectomy and three patients with subtotal hemispherectomy were examined and compared with age-matched normal controls. Apparent diffusion coefficient and fractional anisotropy values were measured in regions along the corticospinal tract: internal capsule, cerebral peduncle, rostral pons, midpons, and caudal pons. None of the patients with anatomic hemispherectomy or subtotal hemispherectomy showed significant changes in either apparent diffusion coefficient or fractional anisotropy values in the corticospinal tract contralateral to the resected hemisphere, whereas increased apparent diffusion coefficient and decreased fractional anisotropy were observed in the ipsilateral rostral pons, midpons, and caudal pons of all patients with anatomic hemispherectomy, as well as in the ipsilateral cerebral peduncle of one patient with subtotal hemispherectomy. Increased apparent diffusion coefficient values were also noted in the ipsilateral internal capsule of the same patient. This study revealed no evidence of significant reinforcement of the contralateral corticospinal tract in patients with hemispherectomy, at least from diffusion tensor imaging measurements, but suggests that wallerian degeneration most likely occurs in the ipsilateral motor pathway.

OBJECTIVES/OBJECTIVE:We previously reported that children who were subjected to early socioemotional deprivation in Romanian orphanages showed glucose hypometabolism in limbic and paralimbic structures, including the orbital frontal gyrus, infralimbic prefrontal cortex, hippocampus/amygdala, lateral temporal cortex, and the brainstem. The present study used diffusion tensor imaging tractography to examine the integrity of white matter tracts that connect these brain regions. METHODS:Fractional anisotropy and apparent diffusion coefficient for uncinate fasciculus, stria terminalis, fornix, and cingulum were measured in 7 right-handed children (5 girls and 2 boys; mean age: 9.7 +/- 2.6 years) with a history of early severe socioemotional deprivation in Eastern European orphanages and compared with similar measurements in 7 right-handed normal children (4 girls and 3 boys; mean age: 10.7 +/- 2.8 years). RESULTS:Neuropsychological assessment of the orphans verified the relatively mild specific cognitive impairment and impulsivity consistent with previous studies of children who were adopted from Romanian orphanages. Fractional anisotropy values in the left uncinate fasciculus were decreased significantly in the early deprivation group compared with control subjects. Apparent diffusion coefficient values for the early deprivation group tended to be greater than that in control subjects in all of the tracts measured, without reaching statistical significance. CONCLUSION/CONCLUSIONS:Our study demonstrates in children who experienced socioemotional deprivation a structural change in the left uncinate fasciculus that partly may underlie the cognitive, socioemotional, and behavioral difficulties that commonly are observed in these children.

Buspirone is used to treat generalized anxiety disorder in children and may be useful in developmental disorders in which brain serotonin synthesis is altered. Autistic children (13 boys, 7 girls) were given a single oral dose of 2.5 mg (2-3 years) or 5.0 mg (4-6 years). Blood was collected for 8 hours, and plasma was assayed for buspirone and its metabolite 1-pyrimidinylpiperazine (1-PP). The peak concentration of buspirone averaged 1141 +/- 748 pg/mL with a time to maximum concentration of 0.8 hours. Half-life was 1.6 +/- 0.3 hours. Peak concentrations of 1-PP were 4.5-fold higher than for buspirone. Girls had higher peak concentrations (1876 vs 746 pg/mL) for buspirone and a lower peak 1-PP/buspirone concentration ratio. These results suggest that buspirone is rapidly absorbed and eliminated in young children with extensive metabolism to 1-PP. Plasma concentrations with 2.5- to 5.0-mg doses were similar to those observed in older children receiving 7.5- to 15-mg doses.

Abnormal metabolism of tryptophan has been implicated in modulation of tumor cell proliferation and immunoresistance. alpha-[(11)C]Methyl-L-tryptophan (AMT) is a PET tracer to measure cerebral tryptophan metabolism in vivo. In the present study, we have measured tumor tryptophan uptake in 40 patients with primary brain tumors using AMT PET and standard uptake values (SUV). Tryptophan metabolism was further quantified in 23 patients using blood input data. Estimates of the volume of distribution (VD') and the metabolic rate constant (k(3)') were calculated and related to magnetic resonance imaging (MRI) and histology findings. All grade II to IV gliomas and glioneuronal tumors showed increased AMT SUV, including all recurrent/residual tumors. Gadolinium enhancement on MRI was associated with high VD' values, suggesting impaired blood-brain barrier, while k(3)' values were not related to contrast enhancement. Low-grade astrocytic gliomas showed increased tryptophan metabolism, as measured by k(3)'. In contrast, oligodendrogliomas showed high VD' values but lower k(3)' as compared with normal cortex. In astrocytic tumors, low grade was associated with high k(3)' and lower VD', while high-grade tumors showed the reverse pattern. The findings show high AMT uptake in primary and residual/recurrent gliomas and glioneuronal tumors. Increased AMT uptake can be due to increased metabolism of tryptophan and/or high volume of distribution, depending on tumor type and grade. High tryptophan metabolic rates in low-grade tumors may indicate activation of the kynurenine pathway, a mechanism regulating tumor cell growth. AMT PET might be a useful molecular imaging method to guide therapeutic approaches aimed at controlling tumor cell proliferation by acting on tryptophan metabolism.