Neurobehavioral comorbidities of pediatric epilepsies are linked to thalamic structural abnormalities.

PURPOSE: Neurobehavioral comorbidities are common in pediatric epilepsy with enduring adverse effects on functioning, but their neuroanatomic underpinning is unclear. Striatal and thalamic abnormalities have been associated with childhood-onset epilepsies, suggesting that epilepsy-related changes in the subcortical circuit might be associated with the comorbidities of children with epilepsy. We aimed to compare subcortical volumes and their relationship with age in children with complex partial seizures (CPS), childhood absence epilepsy (CAE), and healthy controls (HC). We examined the shared versus unique structural-functional relationships of these volumes with behavior problems, intelligence, language, peer interaction, and epilepsy variables in these two epilepsy syndromes. METHODS: We investigated volumetric differences of caudate, putamen, pallidum, and thalamus in children with CPS (N = 21), CAE (N = 20), and HC (N = 27). Study subjects underwent structural magnetic resonance imaging (MRI), intelligence, and language testing. Parent-completed Child Behavior Checklists provided behavior problem and peer interaction scores. We examined the association of age, intelligence quotient (IQ), language, behavioral problems, and epilepsy variables with subcortical volumes that were significantly different between the children with epilepsy and HC. KEY FINDINGS: Both children with CPS and CAE exhibited significantly smaller left thalamic volume compared to HC. In terms of developmental trajectory, greater thalamic volume was significantly correlated with increasing age in children with CPS and CAE but not in HC. With regard to the comorbidities, reduced left thalamic volumes were related to more social problems in children with CPS and CAE. Smaller left thalamic volumes in children with CPS were also associated with poor attention, lower IQ and language scores, and impaired peer interaction. SIGNIFICANCE: Our study is the first to directly compare and detect shared thalamic structural abnormalities in children with CPS and CAE. These findings highlight the vulnerability of the thalamus and provide important new insights on its possible role in the neurobehavioral comorbidities of childhood-onset epilepsy.

A minimum of 3 months of dietary fish oil supplementation is required to raise amygdaloid afterdischarge seizure thresholds in rats--implications for treating complex partial seizures.

Complex partial seizures, which typically originate in limbic structures such as the amygdala, are often resistant to antiseizure medications. Our goal was to investigate the effects of chronic dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) derived from fish oil on seizure thresholds in the amygdala, as well as on blood and brain PUFA levels. The acute effects of injected n-3 PUFAs--eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)--were also tested in the maximal pentylenetetrazol (PTZ) seizure model. In amygdala-implanted subjects, fish oil supplementation significantly increased amygdaloid afterdischarge thresholds, as compared with controls at 3, 5, and 7 months after the start of supplementation. Fish oil supplementation also increased serum EPA and DHA concentrations. DHA concentration in the pyriform-amygdala area increased in the fish-oil treated group by 17-34%, but this effect did not reach statistical significance (P=0.065). DHA significantly increased the latency to seizure onset in the PTZ seizure model, whereas EPA had no significant effect. These observations suggest that chronic dietary fish oil supplementation can raise focal amygdaloid seizure thresholds and that this effect is likely mediated by DHA rather than by EPA.

Slow cortical dynamics and the accumulation of information over long timescales.

Making sense of the world requires us to process information over multiple timescales. We sought to identify brain regions that accumulate information over short and long timescales and to characterize the distinguishing features of their dynamics. We recorded electrocorticographic (ECoG) signals from individuals watching intact and scrambled movies. Within sensory regions, fluctuations of high-frequency (64-200 Hz) power reliably tracked instantaneous low-level properties of the intact and scrambled movies. Within higher order regions, the power fluctuations were more reliable for the intact movie than the scrambled movie, indicating that these regions accumulate information over relatively long time periods (several seconds or longer). Slow (<0.1 Hz) fluctuations of high-frequency power with time courses locked to the movies were observed throughout the cortex. Slow fluctuations were relatively larger in regions that accumulated information over longer time periods, suggesting a connection between slow neuronal population dynamics and temporally extended information processing.

Temporal resolution deficits in patients with refractory complex partial seizures and mesial temporal sclerosis (MTS).

We studied the temporal resolution ability in patients with refractory complex partial seizures and mesial temporal sclerosis (MTS) using Gaps-In-Noise (GIN) test in a prospective cross-sectional study. Thirteen patients with right MTS (age: 31±7.67 years; M:F=8:5) and 13 patients with left MTS (age: 25.76±8.26 years; M:F=9:4) having normal hearing and mini-mental state examination (MMSE) score of >23/30 were recruited. Fifty healthy volunteers (26.3±5.17 years; M:F=28:22) formed the control group. Gaps-In-Noise test demonstrated impaired temporal resolution: 69.2% of patients with right MTS (RMTS) and 76.9% of patients with left MTS (LMTS) had abnormal scores in the right ear for gap detection threshold (GDT) measure. Similarly, 53.8% of patients in the RMTS group and 76.9% of patients in the LMTS group had abnormal scores in the left ear. In percentage of correct identification (PCI), 46.1% of patients with RMTS and 69.2% of patients with LMTS had poorer scores in the right ear, whereas 46.1% of patients with RMTS and 61.5% of patients with LMTS had poorer scores in the left ear. Both patient groups, viz., RMTS and LMTS, demonstrated bilateral temporal resolution deficits.

Validation of connectivity-based thalamic segmentation with direct electrophysiologic recordings from human sensory thalamus.

Connectivity-based segmentation has been used to identify functional gray matter subregions that are not discernable on conventional magnetic resonance imaging. However, the accuracy and reliability of this technique has only been validated using indirect means. In order to provide direct electrophysiologic validation of connectivity-based thalamic segmentations within human subjects, we assess the correlation of atlas-based thalamic anatomy, connectivity-based thalamic maps, and somatosensory evoked thalamic potentials in two adults with medication-refractory epilepsy who were undergoing intracranial EEG monitoring with intrathalamic depth and subdural cortical strip electrodes. MRI with atlas-derived localization was used to delineate the anatomic boundaries of the ventral posterolateral (VPL) nucleus of the thalamus. Somatosensory evoked potentials with intrathalamic electrodes physiologically identified a discrete region of phase reversal in the ventrolateral thalamus. Finally, DTI was obtained so that probabilistic tractography and connectivity-based segmentation could be performed to correlate the region of thalamus linked to sensory areas of the cortex, namely the postcentral gyrus. We independently utilized these three different methods in a blinded fashion to localize the "sensory" thalamus, demonstrating a high-degree of reproducible correlation between electrophysiologic and connectivity-based maps of the thalamus. This study provides direct electrophysiologic validation of probabilistic tractography-based thalamic segmentation. Importantly, this study provides an electrophysiological basis for using connectivity-based segmentation to further study subcortical anatomy and physiology while also providing the clinical basis for targeting deep brain nuclei with therapeutic stimulation. Finally, these direct recordings from human thalamus confirm early inferences of a sensory thalamic component of the N18 waveform in somatosensory evoked potentials.

Hypothalamic ganglioglioma treated by temporal lobectomy. Case report and review of the literature.

The authors report the case of a hypothalamic ganglioglioma with left-sided temporal lobe extension in an 8-year-old girl who presented with seizures. Other cases of ganglioglioma involving the hypothalamus have been reported in the literature; however, this site of origin is exceedingly rare and worthy of report. Treatment involved medial temporal lobectomy with the hypothalamic component of the tumor remaining untouched. The patient recovered postoperatively with no neurological deficits and was seizure free at 12 months. Neither radio- nor chemotherapy was recommended because of the tumor histology, location, and the patient's age. The authors recommend follow up and surgical treatment for possible tumor recurrence. The prognosis for hypothalamic ganglioglioma is unknown.

Long latency evoked potentials in a case of corpus callosum agenesia.

Following monoaural stimulation, long latency auditory evoked potentials (LLAEPs) recorded from contralateral temporal areas have a shorter latency and larger amplitude than those recorded from the ipsilateral temporal areas. This observation agrees with the operational model drawn up in 1967 by Kimura, which assumes that only anatomically prevailing crossed auditory pathways are active during dichotic hearing, while direct pathways are inhibited. The inputs may then be conveyed to the contralateral cortex, from where they finally reach the ipsilateral temporal areas by means of interhemispheric commissures. It is this mechanism which may underline the right ear advantage for verbal stimuli and the left ear advantage for melodies observed when administering dichotic listening tasks. With the aim of verifying this hypothesis, we recorded temporal LLAEPs in a 21 year-old woman suffering from complex partial seizures, whose CT scan and MRI showed corpus callosum agenesia. Our data support the hypothesis that ipsilateral pathways are greatly inhibited by the contralateral pathways, and therefore auditory stimuli can be supposed to reach the contralateral auditory cortex from where they are transferred through the corpus callosum to the ipsilateral auditory cortex.

Transient encephalopathy following a single exposure of high-dose methotrexate in a child with acute lymphoblastic leukemia.

An episode of transient encephalopathy after the first course of intravenous high-dose methotrexate (HD-MTX; 1000 mg/m2) was observed in a 4-year-old girl with acute lymphoblastic leukemia. The neurological abnormalities took place 5 days after HD-MTX therapy. She experienced complex partial seizure and left hemiparesis, which resolved spontaneously in 5 days. Cranial computed tomographic scan and magnetic resonance imaging showed multiple low-density lesions in bilateral hemispheres. It is well appreciated that neurotoxicity from MTX follows prolonged exposures, often accompanying or following radiation therapy. To our knowledge, however, there have been no reports that such neurological complications developed following a single exposure of HD-MTX in patients with ALL. Follow-up electroencephalograms showed that she had periodic lateralized epileptiform discharges (PLEDS), suggesting functional deafferentation of cortical neurons following HD-MTX. Moreover, the serum and CSF MTX levels following a second low-dose course and her clinical course suggested that she had presumably central nervous system leukemia at the time of HD-MTX therapy, which might have been related to neurological complications. The pathogenesis of MTX-induced neurotoxicity is discussed.

Gelastic seizures treated by resection of a hypothalamic hamartoma.

A 7-year-old girl presented for evaluation of a peculiar kind of epilepsy. Her seizures began before 1 year of age and consisted of episodes of brief, uncontrolled and unprovoked laughter than with time progressed to include cursive, complex partial and generalized tonic-clonic seizures. Progressive impairment of cognitive functions was noted as well as precocious puberty. Neuroimaging examination disclosed a hypothalamic hamartoma. It was excised by a pterional approach, and no further seizures were noted. The authors propose direct surgery for the hypothalamic hamartoma as a treatment for this progressive syndrome.