John S. Archer

Cortical/subcortical BOLD changes associated with epileptic discharges: An EEG-fMRI study at 3 T

Background: Malformations of cortical development have characteristic interictal discharges, yet the mechanisms of generation of these discharges are not known in humans. Interictal discharges in malformations of cortical development were studied with EEG-fMRI. Methods: Six subjects with malformations of cortical development and seizures were studied using spike-triggered fMRI at 3 T. The blood oxygen level–dependent (BOLD) signal changes associated with interictal discharges were measured. Results: All subjects showed spike-related BOLD signal changes. In four subjects, the signal increases were seen in the lesion, and in four subjects, decreases were seen surrounding the lesion. Five subjects had BOLD signal changes at distant cortical sites and three had subcortical changes (basal ganglia, reticular formation, or thalamic). Conclusion: BOLD signal changes may be directly correlated with overall synaptic activity. Changes were found in and around the lesion of malformations of cortical development and in distant cortical and subcortical structures. The results suggest that EEG-fMRI studies might help elucidate the mechanisms of epileptic discharges in humans.

Spike-triggered fMRI in reading epilepsy Involvement of left frontal cortex working memory area

Objective: To determine the origin of epileptiform activity in reading epilepsy (RE) and the association between these regions and regions activated by reading, and to assess brain morphometry in these areas. Methods: In two subjects with RE, EEG was recorded inside the three tesla MRI while subjects read silently. Spike-triggered fMRI images were compared to baseline. In a second fMRI study, 30 seconds of silent reading was compared to visual fixation. Morphometry of these areas was assessed using curvilinear surface reconstruction. Left central sulcal patterns in three subjects with RE were compared to three subjects with idiopathic generalized epilepsy (IGE) and 12 normal controls. Results: One subject with RE showed spike-related activity (17 spikes) in the left precentral gyrus, and bilaterally in the central sulcus and globus pallidus. The other showed no definite activation owing to low spike numbers (4 spikes). In both subjects, the block reading task recruited normal visual and language areas including the left posterior middle frontal gyrus. Two subjects with RE showed an unusual gyrus branching anteriorly off the left central sulcus. A similar sulcal pattern was seen in none of the subjects with IGE and only 1 of 12 controls. Conclusion: Spike activity overlapped with reading activity in the left middle frontal gyrus, a structure recruited during working memory cognitive tasks. The authors postulate that, because of a local structural anomaly, the spikes of reading epilepsy spread from working memory areas into adjacent motor cortex, activating a cortical subcortical circuit.

Neuropsychological and functional MRI studies provide converging evidence of anterior language dysfunction in BECTS

Purpose:  Benign childhood epilepsy with centrotemporal spikes (BECTS) is the most common epilepsy syndrome of childhood and can be associated with language difficulties. The exact profile of these difficulties and their neurofunctional underpinnings, however, are not yet clear.

Idiopathic generalised epilepsy of adult onset: clinical syndromes and genetics

Objective: To study the clinical features and genetics of idiopathic generalised epilepsy (IGE) beginning in adult life. Methods: Consecutive patients with IGE, defined as generalised seizures with spike or polyspike and wave on EEG, were studied in the setting of a first seizure clinic where an early postictal EEG record is part of the protocol. Patients were divided into two groups: “classical IGE” with onset before 20 years and inclusive of all the IGE subsyndromes recognised by the international classification; and “adult onset IGE”, when seizure onset was at age 20 years or later. Seizure patterns, clinical features, and genetics of the adult onset group were examined. Results: Of 121 patients with an electro-clinical diagnosis of IGE, 34 (28%) were diagnosed as adult onset IGE. The seizure patterns in these 34 cases were tonic–clonic seizures + absences (3), tonic–clonic seizures + myoclonus (6), and tonic–clonic seizures alone (25). Tonic–clonic seizures were often precipitated by alcohol or sleep deprivation. The proportion of affected first and second degree relatives did not differ between the classical and adult onset IGE groups. Twenty adult onset cases were treated with sodium valproate, four with other antiepileptic drugs, and 10 were untreated. Follow up of 32 of the 34 cases (for 31 (22) months (mean (SD)) showed that tonic–clonic seizures recurred in eight patients: five with identified provocative factors and three without. Conclusions: Adult onset IGE is a relatively frequent and benign disorder. Seizures are usually provoked and are easy to control. Patients in this age group may often be misdiagnosed as having non-lesional partial epilepsy. Early postictal EEG and sleep deprivation studies may improve the detection of these patients. Pedigree analysis suggests that adult onset IGE, like classical IGE, has a genetic aetiology.

Benign Epilepsy with Centro-temporal Spikes : Spike Triggered fMRI Shows Somato-sensory Cortex Activity

Summary:  Objective: We performed spike triggered functional MRI (fMRI) in a 12 year old girl with Benign Epilepsy with Centro‐temporal Spikes (BECTS) and left‐sided spikes. Our aim was to demonstrate the cerebral origin of her interictal spikes.

Focal epileptiform spikes do not show a canonical BOLD response in patients with benign rolandic epilepsy (BECTS).

Simultaneous EEG and functional MRI (EEG-fMRI) studies of focal epileptiform spikes commonly use the canonical haemodynamic response function (HRF) to model the blood-oxygenation-level-dependent (BOLD) response to these events. Support for the use of the canonical HRF has come from large studies that contain mixed cohorts of epilepsy syndromes and discharge types, and has demonstrated plausible epileptic localisation results in the majority of patients. Other studies, however, have reported that some patients show a BOLD response that differs markedly from a canonical HRF. Our aim in this study was to see if the BOLD response is well modelled by a canonical HRF in a homogeneous cohort of patients with benign epilepsy with centrotemporal spikes (BECTS), an idiopathic partial epilepsy with stereotypical centrotemporal spikes on the EEG. We studied eight well-characterised and typical BECTS patients and found that the shape of the average BOLD response was different to the canonical HRF. Furthermore, a localisation analysis using the group-average response provided increased sensitivity and specificity compared to the canonical HRF. Our findings suggest that the canonical HRF may not provide the best model for the BOLD response in some epilepsy syndromes or spike-types. In studies of homogeneous patient groups, therefore, localisation results may be improved by using a group-specific BOLD response.

A Sheep Model for the Study of Focal Epilepsy with Concurrent Intracranial EEG and Functional MRI

Summary:  Purpose: We describe a sheep model of penicillin‐induced seizure activity using electroencephalography (EEG) and functional MRI (fMRI).

Murray Valley encephalitis: a review of clinical features, diagnosis and treatment

Murray Valley encephalitis virus (MVEV) is a mosquito‐borne virus that is found across Australia, Papua New Guinea and Irian Jaya.

Networks underlying paroxysmal fast activity and slow spike and wave in Lennox-Gastaut syndrome

Objective: To use EEG-fMRI to determine which structures are critically involved in the generation of paroxysmal fast activity (PFA) and slow spike and wave (SSW) (1.5–2.5 Hz), the characteristic interictal discharges of Lennox-Gastaut syndrome (LGS). Methods: We studied 13 well-characterized patients with LGS using structural imaging and EEG-fMRI at 3 tesla. Ten patients had cortical structural abnormalities. PFA and SSW were considered as separate events in the fMRI analysis. Results: Simultaneous with fMRI, PFA was recorded in 6 patients and SSW in 9 (in 2, both were recorded). PFA events showed almost uniform increases in blood oxygen level–dependent (BOLD) signal in “association” cortical areas, as well as brainstem, basal ganglia, and thalamus. SSW showed a different pattern of BOLD signal change with many areas of decreased BOLD signal, mostly in primary cortical areas. Two patients with prior callosotomy had lateralized as well as generalized PFA. The lateralized PFA was associated with a hemispheric version of the PFA pattern we report here. Conclusion: PFA is associated with activity in a diffuse network that includes association cortices as well as an unusual pattern of simultaneous activation of subcortical structures (brainstem, thalamus, and basal ganglia). By comparison, the SSW pattern is quite different, with cortical and subcortical activations and deactivations. Regardless of etiology, it appears that 2 key, but distinct, patterns of diffuse brain network involvement contribute to the defining electrophysiologic features of LGS.

A neurodevelopmental basis for BECTS: evidence from structural MRI.

PURPOSE BECTS (benign epilepsy with centro-temporal spikes) is one of the most common childhood-onset epilepsy syndromes. We investigated quantitative evidence for brain morphological variation associated with BECTS to provide insights into the neuroanatomical basis of this disorder. METHODS Three independent BECTS groups were imaged at different stages: (a) near onset (n=16, mean age 9.3±1.6 years), (b) ~9 years after onset (n=9, mean age 15.8±2.3 years), and (c) ~15 years after onset (n=10, mean age 22.7±2.7 years). Age-matched controls were imaged with each group. Whole brain T1-weighted MRI was acquired. Voxel-based morphometry (groups a-c) and cortical thickness analyses (groups b and c) were undertaken within each group and for the groups combined. The relationship between cortical morphology and age was investigated. KEY FINDINGS The voxel-based morphometry analysis indicated increased bilateral grey matter volume in the superior frontal gyrus, insula and right inferior frontal gyrus regions in BECTS. The magnitude of the increase lessened with age of the cases. Cortical thickness analysis revealed thicker cortex in BECTS along middle and inferior frontal gyri bilaterally, left insula and bilateral supramarginal gyrus in the 9-year-after-onset group, that normalised with age. The rate of cortical thickness changes with age were greater in BECTS cases than in controls. SIGNIFICANCE Increased cortical gray matter associated with BECTS was found. The decreasing magnitude of the effect with increasing age parallels the natural history of the disorder. The areas affected are consistent with neurocognitive dysfunction in BECTS.