Donald W. Gross

The BOLD response to interictal epileptiform discharges.

We studied single-event and average BOLD responses to EEG interictal epileptic discharges (IEDs) in four patients with focal epilepsy, using continuous EEG-fMRI during 80-min sessions. The detection of activated areas was performed by comparing the BOLD signal at each voxel to a model of the expected signal. Since little is known about the BOLD response to IEDs, we modeled it with the response to brief auditory events (G. H., NeuroImage 9, 416-429). For each activated area, we then obtained the time course of the BOLD signal for the complete session and computed the actual average hemodynamic response function (HRF) to IEDs. In two of four patients, we observed clear BOLD responses to single IEDs. The average response was composed of a positive lobe peaking between 6 and 7 s in all patients and a negative undershoot in three patients. There were important variations in amplitude and shape between average HRFs across patients. The average HRF presented a wider positive lobe than the Glover model in three patients and a longer undershoot in two. There was a remarkable similarity in the shape of the HRF across areas for patients presenting multiple activation sites. There was no clear correlation between the amplitude of individual BOLD responses and the amplitude of the corresponding EEG spike. The possibility of a longer HRF could be used to improve statistical detection of activation in simultaneous EEG-fMRI. The variability in average HRFs across patients could reflect in part different pathophysiological mechanisms.

In Vivo Diffusion Tensor Imaging and Histopathology of the Fimbria-Fornix in Temporal Lobe Epilepsy

While diffusion tensor imaging (DTI) has been extensively used to infer micro-structural characteristics of cerebral white matter in human conditions, correlations between human in vivo DTI and histology have not been performed. Temporal lobe epilepsy (TLE) patients with mesial temporal sclerosis (MTS) have abnormal DTI parameters of the fimbria-fornix (relative to TLE patients without MTS) which are presumed to represent differences in axonal/myelin integrity. Medically intractable TLE patients who undergo temporal lobe resection including the fimbria-fornix provide a unique opportunity to study the anatomical correlates of water diffusion abnormalities in freshly excised tissue. Eleven patients with medically intractable TLE were recruited (six with and five without MTS) for presurgical DTI followed by surgical excision of a small specimen of the fimbria-fornix which was processed for electron microscopy. Blinded quantitative analysis of the microphotographs included axonal diameter, density and area, cumulative axon membrane circumference, and myelin thickness and area. As predicted by DTI the fimbria-fornix of TLE patients with MTS had increased extra-axonal fraction, and reduced cumulative axonal membrane circumference and myelin area. Consistent with the animal literature, water diffusion anisotropy over the crus of the fimbria-fornix was strongly correlated with axonal membranes (cumulative membrane circumference) within the surgical specimen (∼15% of what was analyzed with DTI). The demonstration of a correlation between histology and human in vivo DTI, in combination with the observation that in vivo DTI accurately predicted white matter abnormalities in a human disease condition, provides strong validation of the application of DTI as a noninvasive marker of white matter pathology.

Extratemporal white matter abnormalities in mesial temporal lobe epilepsy demonstrated with diffusion tensor imaging.

Summary:u2002 Purpose: Recent studies have demonstrated bilateral white matter abnormalities in temporal lobe epilepsy (TLE) patients with unilateral mesial temporal sclerosis (MTS). The purpose of this project was to determine whether abnormalities of water diffusion are seen in extratemporal white matter of patients with TLE and pathologically confirmed MTS and to determine whether these findings are associated with worse surgical outcome.

Correlation of high-frequency oscillations with the sleep-wake cycle and cognitive activity in humans.

While several authors have suggested that high-frequency electroencephalogram activity (gamma, >30 Hz) correlates with conscious thought, others have suggested that electroencephalogram activity >30 Hz shows the same relationships to cognitive activity and sleep as activity in the conventional beta frequency band. The existence of coherence of gamma over large distances also remains controversial. We studied quantitatively the relationship of gamma activity to the sleep-wake cycle and cognitive tasks during wakefulness in humans using intracranial electroencephalogram. Gamma activity made up less than 1% of the total power spectrum. A significant relationship was observed between gamma activity and the sleep-wake cycle such that gamma was highest during wakefulness, intermediate during light and rapid eye movement sleep, and lowest during slow-wave sleep. As well, gamma was higher during rapid eye movement sleep with eye movements than during rapid eye movement sleep without eye movements. During a cognitive task experiment, while lower frequencies, including beta, showed a stepwise reduction with increasing task difficulty, gamma was observed to increase during cognitive tasks as compared to the resting state. The relationship between gamma and the sleep-wake cycle and cognitive tasks was independent of brain region and hemisphere. Coherence of gamma activity at distances of 5 mm and greater was not observed. Our data support previously reported findings that gamma activity has a significant relationship to the sleep-wake cycle. The findings of differences in gamma during REM sleep with and without eye movements suggest that the presence or absence of eye movements may reflect two different states of brain activity. Our findings of differences in the relationships of the beta and gamma bands to both the sleep-wake cycle and cognitive tasks demonstrate that various components of the high-frequency spectrum behave differently in some situations.

α-[11C]-Methyl-l-tryptophan PET identifies the epileptogenic tuber and correlates with interictal spike frequency

Epilepsy surgery has been successfully performed in patients with tuberous sclerosis complex (TSC) and seizures arising from a restricted epileptogenic area. The outcome of cortical excision depends on accurate pre-surgical identification of the epileptogenic tuber. [11C] alpha-methyl-L-tryptophan (alpha-MTrp) was originally developed to measure serotonin synthesis in vivo with positron emission tomography (PET). However in pathologic conditions its uptake may also depend on the synthesis of quinolinic or kynurenic acid via the kynurenine pathway. Increased levels of serotonin and quinolinic acid have been observed in epileptogenic lesions, raising the possibility that alpha-MTrp PET may localize the epileptogenic area. The aim of this study was to correlate alpha-MTrp PET uptake with the localization of the epileptogenic area and with interictal spike frequency in patients with TSC. alpha-MTrp uptake was measured in 8 patients (2 males, mean age 29.6+/-14.9 years, range 3-50 years) with intractable partial epilepsy due to TSC. All patients underwent scalp EEG monitoring during the PET scan. In four (50%), increased uptake of alpha-MTrp occurred in the epileptogenic area alone. Two (25%) patients showed multifocal abnormalities and the remaining two (25%) did not show focal changes. PET localization was mostly seen in patients with frequent interictal abnormalities on the EEG. Furthermore, there was a significant correlation between alpha-MTrp uptake and the frequency of interictal spikes (r=0.6; P<0.05). alpha-MTrp PET is a promising diagnostic tool in the localization of the epileptogenic area in patients with TSC.

Reversible coma: a rare presentation of spontaneous intracranial hypotension.

BACKGROUNDnSpontaneous intracranial hypotension (SIH) is a well-recognized neurologic disorder that typically presents with orthostatic headaches, low cerebral spinal fluid pressures and distinct abnormalities on magnetic resonance imaging.nnnMETHODSnWe present a case of a rare presentation of SIH.nnnRESULTSnA 49-year-old man presented with a two week history of orthostatic headaches that rapidly progressed to encephalopathy and coma, requiring intubation. Neuroimaging revealed abnormalities typical of SIH; diffusely enhancing pachymeninges, subdural fluid collections, and descent of the brain. Treatment with an epidural blood patch reversed his coma within minutes. Following a second blood patch, the patient became asymptomatic. No cerebral spinal leak could be identified on magnetic resonance imaging or on a nuclear medicine technetium cerebral spinal fluid flow study. At six month follow-up, he remained symptom free.nnnCONCLUSIONnThe mechanism of coma in SIH is presumed to be compression of the diencephalon from downward displacement of the brain. Although it is very unusual for patients with SIH to present with coma, it is important to recognize since the coma may be reversible with epidural blood patches.

Diffusion tensor imaging abnormalities in focal cortical dysplasia

PURPOSEnFocal cortical dysplasia (FCD) is one of the most common underlying pathologic substrates in patients with medically intractable epilepsy. While magnetic resonance imaging (MRI) evidence of FCD is an important predictor of good surgical outcome, conventional MRI is not sensitive enough to detect all lesions. Previous reports of diffusion tensor imaging (DTI) abnormalities in FCD suggest the potential of DTI in the detection of FCD. The purpose of this study was to study subcortical white matter underlying small lesions of FCD using DTI.nnnMETHODSnFive patients with medically intractable epilepsy and FCD were investigated. Diffusion tensor imaging images were acquired (20 contiguous 3 mm thick axial slices) with maps of fractional anisotropy (FA), trace apparent diffusion coefficient (trace/3 ADC), and principal eigenvalues (ADC parallel and ADC perpendicular to white matter tracts) being calculated for each slice. Region of interest analysis was used to compare subcortical white matter ipsilateral and contralateral to the lesion.nnnRESULTSnThree subjects with FCD associated with underlying white matter hyperintensities on T2 weighted MRI were observed to have increased trace/3 ADC, reduced fractional anisotropy and increased perpendicular water diffusivity which was greater than the relative increase in the parallel diffusivity. No DTI abnormalities were identified in two patients with FCD without white matter hyperintensities on conventional T2-weighted MRI.nnnCONCLUSIONSnWhile DTI abnormalities in FCD with obvious white matter involvement are consistent with micro-structural degradation of the underlying subcortical white matter, DTI changes were not identified in FCD lesions with normal appearing white matter.

Intracranial EEG with Very Low Frequency Activity Fails to Demonstrate an Advantage Over Conventional Recordings

Summary: Purpose: Conventional scalp and intracranial EEG is recorded within a limited band of frequencies (0.3–70 Hz) based on the premise that clinically relevant cerebral activity occurs within this frequency range. Ikeda et al. recently demonstrated focal very low frequency activity (VLFA), <0.3 Hz, at seizure onset for both intra‐ and extracranial recordings. The purpose of this investigation was prospectively to study VLFA during seizures in intracranial recordings to determine whether activity in this frequency range provides useful information regarding localization of seizure onset and spread.

EEG telemetry with closely spaced electrodes in frontal lobe epilepsy.

The use of additional electrodes (other than standard 10-20 electrodes) has proved to be extremely useful in the investigation of patients with temporal lobe epilepsy. The development of 32- and 64-channel EEG machines, along with the reformatting capabilities of digital EEG has greatly increased the possibilities in the number of electrodes and recording montages. The authors wanted to determine whether the use of closely spaced electrodes designed to increase the coverage of frontocentral regions is of benefit in the investigation of patients with frontocentral epilepsy. Patients investigated for frontocentral epilepsy underwent EEG telemetry with closely spaced electrodes based on the 10-10 nomenclature. Twenty-three patients were studied. An additional 30 minutes was required by technicians to create the montage. Unilateral frontal or frontocentral epileptic abnormalities were observed in 10 patients, independent bifrontal in 5 patients, synchronous bifrontal in 4 patients, and no EEG changes in 4 patients. In no patient did the addition of closely spaced electrodes lead to a change in the classification of the EEG. Closely spaced electrodes did not reveal focal abnormalities, which were not already apparent with 10-20 electrodes, nor did they demonstrate evidence of laterality in bilaterally synchronous discharges.

Status Epilepticus Presenting in a Patient with Neurosyphilis and a Previously Asymptomatic Arachnoid Cyst

To the Editor: Primavera et al. (1) described a series of four patients with neurosyphilis with status epilepticus (SE) as the first manifestation of their infection. We report a similar presentation in a man with a previously asymptomatic arachnoid cyst. A 44-year-old man had been previously healthy. For two months prior to his admission, relatives noted mild word-finding difficulties with a slight deterioration in verbal fluency. The evening before his admission he had loss of dexterity in his right hand while using chopsticks at a restaurant. Several hours later, he was found convulsing by his wife. There was no history of previous seizures, head trauma, or serious infections (including syphilis-associated skin lesions). On arrival to the emergency department, he had been