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1.  Vitamin-Responsive Epileptic Encephalopathies in Children 
Untreated epileptic encephalopathies in children may potentially have disastrous outcomes. Treatment with antiepileptic drugs (AEDs) often may not control the seizures, and even if they do, this measure is only symptomatic and not specific. It is especially valuable to identify potential underlying conditions that have specific treatments. Only a few conditions have definitive treatments that can potentially modify the natural course of disease. In this paper, we discuss the few such conditions that are responsive to vitamin or vitamin derivatives.
doi:10.1155/2013/510529
PMCID: PMC3745849  PMID: 23984056
2.  Functional MRI of Sleep Spindles and K-complexes 
Clinical Neurophysiology  2011;123(2):303-309.
Objective
Sleep spindles and K-complexes are EEG hallmarks of non-REM sleep. However, the brain regions generating these discharges and the functional connections of their generators to other regions are not fully known. We investigated the neuroanatomical correlates of spindles and K-complexes using simultaneous EEG and fMRI.
Methods
EEGs recorded during EEG-fMRI studies of 7 individuals were used for fMRI analysis. Higher-level group analyses were performed, and images were thresholded at Z≥2.3.
Result
fMRI of 106 spindles and 60 K-complexes was analyzed. Spindles corresponded to increased signal in thalami and posterior cingulate, and right precuneus, putamen, paracentral cortex, and temporal lobe. K-complexes corresponded to increased signal in thalami, superior temporal lobes, paracentral gyri, and medial regions of the occipital, parietal and frontal lobes. Neither corresponded to regions of decreased signal.
Conclusions
fMRI of both spindles and K-complexes depicts signal subjacent to the vertex, which likely indicates each discharges’ source. The thalamic signal is consistent with thalamic involvement in sleep homeostasis. The limbic region’s signal is consistent with roles in memory consolidation. Unlike the spindle, the K-complex corresponds to extensive signal in primary sensory cortices.
Significance
Identification of these active regions contributes to the understanding of sleep networks and the physiology of awareness and memory during sleep.
doi:10.1016/j.clinph.2011.06.018
PMCID: PMC3208090  PMID: 21775199
electroencephalography (EEG); functional MRI (fMRI); spindles; K-complexes; sleep; non-REM
3.  Memory Enhancement and Deep-Brain Stimulation of the Entorhinal Area 
The New England journal of medicine  2012;366(6):502-510.
BACKGROUND
The medial temporal structures, including the hippocampus and the entorhinal cortex, are critical for the ability to transform daily experience into lasting memories. We tested the hypothesis that deep-brain stimulation of the hippocampus or entorhinal cortex alters memory performance.
METHODS
We implanted intracranial depth electrodes in seven subjects to identify seizure-onset zones for subsequent epilepsy surgery. The subjects completed a spatial learning task during which they learned destinations within virtual environments. During half the learning trials, focal electrical stimulation was given below the threshold that elicits an afterdischarge (i.e., a neuronal discharge that occurs after termination of the stimulus).
RESULTS
Entorhinal stimulation applied while the subjects learned locations of landmarks enhanced their subsequent memory of these locations: the subjects reached these landmarks more quickly and by shorter routes, as compared with locations learned without stimulation. Entorhinal stimulation also resulted in a resetting of the phase of the theta rhythm, as shown on the hippocampal electroencephalogram. Direct hippocampal stimulation was not effective. In this small series, no adverse events associated with the procedure were observed.
CONCLUSIONS
Stimulation of the entorhinal region enhanced memory of spatial information when applied during learning. (Funded by the National Institutes of Health and the Dana Foundation.)
doi:10.1056/NEJMoa1107212
PMCID: PMC3447081  PMID: 22316444
4.  Functional Imaging of Sleep Vertex Sharp Transients 
Objective
The vertex sharp transient (VST) is an electroencephalographic (EEG) discharge that is an early marker of non-REM sleep. It has been recognized since the beginning of sleep physiology research, but its source and function remain mostly unexplained. We investigated VST generation using functional MRI (fMRI).
Methods
Simultaneous EEG and fMRI were recorded from 7 individuals in drowsiness and light sleep. VST occurrences on EEG were modeled with fMRI using an impulse function convolved with a hemodynamic response function to identify cerebral regions correlating to the VSTs. A resulting statistical image was thresholded at Z>2.3.
Results
Two hundred VSTs were identified. Significantly increased signal was present bilaterally in medial central, lateral precentral, posterior superior temporal, and medial occipital cortex. No regions of decreased signal were present.
Conclusion
The regions are consistent with electrophysiologic evidence from animal models and functional imaging of human sleep, but the results are specific to VSTs. The regions principally encompass the primary sensorimotor cortical regions for vision, hearing, and touch.
Significance
The results depict a network comprising the presumed VST generator and its associated regions. The associated regions functional similarity for primary sensation suggests a role for VSTs in sensory experience during sleep.
doi:10.1016/j.clinph.2010.12.049
PMCID: PMC3105179  PMID: 21310653
electroencephalography (EEG); functional MRI (fMRI); sleep; vertex sharp transients
5.  Referral pattern for epilepsy surgery after evidence-based recommendations 
Neurology  2010;75(8):699-704.
Background:
Class I evidence for surgical effectiveness in refractory temporal lobe epilepsy (TLE) in 2001 led to an American Academy of Neurology practice parameter in 2003 recommending “referral to a surgical epilepsy center on failing appropriate trials of first-line antiepileptic drugs.” We examined whether this led to a change in referral patterns to our epilepsy center.
Methods:
We compared referral data for patients with TLE at our center for 1995 to 1998 (group 1, n = 83) and 2005 to 2008 (group 2, n = 102) to determine whether these recommendations resulted in a change in referral patterns for surgical evaluation. Patients with brain tumors, previous epilepsy surgery evaluations, or brain surgery (including epilepsy surgery) were excluded.
Results:
We did not find a difference between the groups in the duration from the diagnosis of habitual seizures to referral (17.1 ± 10.0 vs 18.6 ± 12.6 years, p = 0.39) or the age at the time of evaluation (34.1 ± 10.3 vs 37.0 ± 11.8 years, p = 0.08). However, there was a difference in the distributions of age at evaluation (p = 0.03) and the duration of pharmacotherapy (p = 0.03) between the groups, with a greater proportion of patients in group 2 with drug-resistant epilepsy both earlier and later in their treatment course. Nonepileptic seizures were referred significantly earlier than TLE in either group or when combined.
Conclusions:
Our analysis does not identify a significantly earlier referral for epilepsy surgery evaluation as recommended in the practice parameter, but suggests a hopeful trend in this direction.
GLOSSARY
= American Academy of Neurology;
= antiepileptic drug;
= Early Randomized Surgical Epilepsy Trial;
= nonepileptic seizures;
= randomized controlled trial;
= temporal lobe epilepsy;
= vagus nerve stimulator.
doi:10.1212/WNL.0b013e3181eee457
PMCID: PMC2931651  PMID: 20733145

Results 1-5 (5)