D W Gross

McGill University, Montréal, Quebec, Canada

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Publications (13)61.88 Total impact

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    ABSTRACT: 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.
    Epilepsy Research 01/2003; 52(3):203-13. DOI:10.1016/S0920-1211(02)00216-4 · 2.19 Impact Factor
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    ABSTRACT: 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.
    NeuroImage 12/2002; 17(3):1182-92. DOI:10.1006/nimg.2002.1164 · 6.13 Impact Factor
  • Epilepsia 08/2002; 43(7):775-6. DOI:10.1046/j.1528-1157.2002.10902.x · 4.58 Impact Factor
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    ABSTRACT: 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. 8, 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.
    NeuroImage 01/2002; 17(3):1182-1192. · 6.13 Impact Factor
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    ABSTRACT: [(11)C] alpha-methyl-L-tryptophan (alpha-MTrp) has been developed as a tracer for the study of the synthesis of serotonin in the brain with PET. However, it has been shown that in pathologic conditions the tracer may reflect the activation of kynurenine metabolism. Increased levels of serotonin and quinolinic acid have been described in resected epileptogenic cortex, raising the possibility that alpha-MTrp can localize seizure foci in patients with intractable partial epilepsy. The authors assessed the uptake of alpha-MTrp in 18 patients (11 men, mean +/- SD age 27.1 +/- 10.1 years, range 13 to 54) with intractable partial epilepsy to correlate the PET findings with the epileptogenic area defined by electroclinical and neuroimaging data. Seven patients with cortical dysplasia (CD) and 11 with partial epilepsy in which conventional MRI and fluorine-18-deoxyglucose ((18)FDG)-PET studies failed to detect any abnormality were studied. All underwent scalp EEG monitoring during the PET scan to exclude ictal events and estimate the interictal epileptic activity. In seven patients (39%; CD four and cryptogenic partial epilepsy three), PET showed focal increased uptake of alpha-MTrp corresponding to the epileptogenic area. alpha-MTrp uptake in the epileptic focus correlated with the frequency of interictal spikes (r = 0.7, p < 0.05). alpha-MTrp-PET may be of value in the localization of the epileptogenic area not only in patients with visible dysplastic lesions, but also in those with cryptogenic partial epilepsy.
    Neurology 12/2001; 57(9):1629-36. DOI:10.1212/WNL.57.9.1629 · 8.30 Impact Factor
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    ABSTRACT: 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.
    Journal of Clinical Neurophysiology 08/2000; 17(4):414-8. DOI:10.1097/00004691-200007000-00007 · 1.60 Impact Factor
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    ABSTRACT: When considering resection of epileptic generators near the central sulcus, it is essential to define the spatial relationship between the epileptic generator and the primary sensorimotor hand area. In this study, the authors assessed the accuracy of dipole modeling of electroencephalographic spikes and median nerve somatosensory evoked potentials (SSEPs) in defining this relationship preoperatively and noninvasively. Epileptic spikes and SSEPs in patients with focal central area epilepsy were represented by dipole models coregistered onto global magnetic resonance images. In patients who underwent surgery, spike dipoles were also compared with findings of electrocorticography (ECoG) and with the resection area. To improve the accuracy of the dipole models, anatomical landmarks of the hand area were used to assess the error in SSEP dipole location, and this error measure was used to correct the location of spike dipoles. Five patients with central epilepsy were studied, three of whom underwent ECoG-guided surgical resections. The location of SSEP dipoles correlated well with anatomical landmarks of the primary sensory hand area. The relative position of the spike and SSEP dipoles correlated well with the patients' ictal symptoms, ECoG findings, and the location of the epileptic focus (as defined by the resection cavity in patients who became seizure free postoperatively). Corrected spike dipoles were located even closer to the resection cavity. The calculation of the relative location of spike and SSEP dipoles is a simple noninvasive method of determining the relationship between the primary hand area and an epileptic focus in the central area. The spatial resolution of this technique can be further improved using easily identifiable anatomical landmarks.
    Journal of Neurosurgery 06/2000; 92(5):785-92. DOI:10.3171/jns.2000.92.5.0785 · 3.23 Impact Factor
  • D W Gross, J Gotman
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    ABSTRACT: 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.
    Neuroscience 11/1999; 94(4):1005-18. DOI:10.1016/S0306-4522(99)00343-7 · 3.33 Impact Factor
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    ABSTRACT: 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. Patients undergoing intracranial electrode implantation were studied by using a high-pass filter of 0.01 Hz. The timing, location, and pattern of seizure onset were first determined by using a digital high-pass filter of 0.3 Hz (conventional seizure onset). Seizures were then reviewed without digital filters and the presence of VLFA recorded, along with its timing and location. Forty-seven seizures were recorded in four patients. VLFA was not observed in 29 seizures and, in one other case, VLFA occurred simultaneous with movement. Of seizures with VLFA (n = 17), the timing and location of VLFA were not consistent with those of conventional seizure onset or propagation. Our study failed to demonstrate any clinical advantage of intracranial telemetry recordings with a high-pass filter of 0.01 Hz over conventional recordings with regard to determining the timing and location of seizure onset and propagation.
    Epilepsia 07/1999; 40(7):891-8. DOI:10.1111/j.1528-1157.1999.tb00795.x · 4.58 Impact Factor
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    ABSTRACT: To study the incidence and pattern of epilepsy in patients with periventricular leukomalacia (PVLM) in two specialty clinic settings. Motor and cognitive deficit as well as epilepsy are common in patients with PVLM. With modern imaging techniques, PVLM is now easily recognized. Epileptic seizures and syndromes as well as motor and cognitive deficits were correlated with MRI findings. Two patient populations were studied: Group A-children with cerebral palsy and PVLM presenting to a center for children with motor disability (n = 19); and Group B-epileptic patients with PVLM presenting to a tertiary epilepsy center (n = 12). A single patient with PVLM and epilepsy who underwent extensive investigations, including intracranial EEG telemetry, is reported. In Group A, 47% of patients had epilepsy (9/19). PVLM was found in 1.27% of patients investigated for epilepsy at a tertiary epilepsy center (12/942). The majority of patients in both groups had multiple seizure types, with complex partial seizures being most common. Of patients with seizures (Groups A and B), 85.7% had intractable epilepsy (18/21). Intracranial EEG in the illustrative case demonstrated a multifocal epileptic process with occipitotemporal predominance. PVLM was an uncommon underlying cause in patients presenting with epilepsy (Group A); however, patients presenting with motor disability and PVLM (Group B) had a high incidence of seizures. PVLM in epileptic patients is associated with multiple seizure types and medically refractory disease.
    Neurology 02/1999; 52(2):341-5. DOI:10.1212/WNL.52.2.341 · 8.30 Impact Factor
  • Donald W. Gross, Barbara E. Jones, Jean Gotman
    Journal of Clinical Neurophysiology 01/1999; 16(2). DOI:10.1097/00004691-199903000-00015 · 1.60 Impact Factor
  • D W Gross, L F Quesney, A F Sadikot
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    ABSTRACT: Periodic lateralized epileptiform discharges have been recognized for 33 years; however, little is known about the underlying mechanism causing periodic discharges. The following case provides an opportunity to study PLEDs in a patient with precisely localized subcortical grey matter lesions. Routine EEGs and overnight polysomnography were performed on the study patient. Standard 10-20 electrode positions were used, as well as EOG and chin EMG for polysomnography. The study patient was a 39-year-old woman with severe left caudate nucleus atrophy and right hemi-dystonia. She had left ventral-lateral (VL) thalamotomies in 1989 and 1991, pallidotomy in 1992, and centromedian thalamic stimulator implantation in 1997. EEGs prior to surgical intervention demonstrated left hemisphere PLEDs during sleep. Following CM nucleus stimulatory implantation, the patient had overnight polsomnography. EEG during wakefulness and REM sleep was normal. With stages I-IV sleep left hemisphere PLEDs at 1-2 Hz were seen with fronto-temporal predominance. Sleep spindles were present bilaterally. There was no history of seizures, before or after surgery. The finding of PLEDs confined to synchronized sleep which were not affected by surgical manipulation of the motor basal ganglia circuit suggests a role of the associative basal ganglia circuit in the generation of periodic phenomenon.
    Electroencephalography and Clinical Neurophysiology 01/1999; 107(6):434-8. DOI:10.1016/S0013-4694(98)00103-5
  • Annals of Neurology 06/1998; 43(5):687. DOI:10.1002/ana.410430525 · 11.91 Impact Factor