Stefano Seri

Extracranial localization of intracranial interictal epileptiform activity using LORETA (low resolution electromagnetic tomography)

Besides the standard clinical methods of EEG waveshape analysis, mathematical models for reconstruction of dipolar sources from the digitized surface EEG have been introduced in epilepsy research. Although useful for localizing focal sources, these methods are inadequate for analyzing widespread epileptiform activity. A recently introduced alternative method called LORETA (low resolution electromagnetic tomography, Pascual-Marqui et al., 1994), directly computes the current distribution throughout the full brain volume, assuming that neighboring neuronal populations are simultaneously and synchronously activated. In mathematical terms the method selects the smoothest of all possible 3-dimensional current distributions, inherently introducing a certain amount of dispersion. In 7 patients, undergoing simultaneous EEG recording from 10 intracranial (subdural) and 22 extracranial electrodes, 111 subdural discharges (61 subtemporal and 50 lateral temporal) were identified. The exact time point of maximal intracranial activity was automatically identified, and the LORETA solution at that timepoint was computed from the surface EEG. Statistical comparison revealed significantly higher LORETA current density in the area corresponding to the subdurally recorded spike compared to other areas, and a more anterior and more medial LORETA location for subtemporal compared to lateral temporal spikes. This study indicates that the LORETA technique may become a useful method to localize electrical activity in the brain.

Autism in tuberous sclerosis: evoked potential evidence for a deficit in auditory sensory processing.

OBJECTIVE Autism is a frequent manifestation of tuberous sclerosis complex (TSC) being reported in up to 60% of the patients. Its presence is in association with cortical and subcortical lesions involving the temporal lobes. This study was designed to shed light on the functional mechanisms linking anatomical lesions of TSC and behavioural phenotype by investigating scalp recorded event related potentials to auditory stimuli. METHODS Fourteen children with TSC, seven of which fulfilled the DSM IV criteria for autistic disorder were selected for this study. All of the subjects underwent high resolution MRI, EEG, brainstem auditory evoked potentials, cognitive and behavioural evaluation. Electrical evoked responses to two different pitches, presented with different probability (80% 1000 Hz, 20% 1500 Hz) were recorded from 21 scalp electrodes in the autistic and non-autistic subgroups, to assess central auditory processing and automatic memory. RESULTS The first component of the long latency auditory response (N1) had a significantly prolonged latency with lower amplitude in all of the patients with autistic behaviour who, contrary to non-autistics had MRI lesions involving one or both temporal lobes. A mismatch negativity was detected in all subjects and had a longer latency in subjects with autistic behaviour. CONCLUSIONS To our knowledge this is the first electrophysiological evidence of a deficit in auditory information processing and automatic memory in TSC patients with autistic behaviour.

Topical Review: Intractable Seizures in Tuberous Sclerosis Complex: From Molecular Pathogenesis to the Rationale for Treatment

Tuberous sclerosis complex is a multisystem autosomal dominant genetic disorder resulting from mutations in one of two genes, TSC1 and TSC2. Pathologically, tuberous sclerosis complex is characterized by abnormal cellular differentiation and proliferation, as well as abnormal neuronal migration. Epilepsy occurs in about 90% of patients, with onset frequently in the first year of life. In a sizable proportion of individuals, seizures tend to be refractory to antiepileptic drug treatment. This article reviews the progress in understanding drug-resistant seizures in tuberous sclerosis complex, from molecular pathogenesis to the pathophysiologic mechanisms of epileptogenesis, and the rationale for appropriate medical and surgical treatment. (J Child Neurol 2005;20:318—325).

Spike-induced interference in auditory sensory processing in Landau-Kleffner syndrome.

OBJECTIVES Landau-Kleffner Syndrome (LKS) is an epileptic syndrome characterised by a deficit in language comprehension and production, paroxysmal epileptiform activity in the posterior temporal leads, and by the inconsistent presence of epileptic fits. Its interest lies in the fact that it stands as a model for the study of interference of epileptiform activity on cognitive function, although the pathophysiology of the decline in language skills that follows its onset has not yet been clarified. METHODS We have recorded spike-triggered auditory evoked responses in a group of 6 children with LKS, to investigate whether the occurrence of individual EEG paroxysms is able per se to induce a decline in the response of the auditory cortex. RESULTS Results have indicated that left hemisphere spikes are associated with a greater reduction in amplitude and an increase in latency of the NI, than spikes occurring in the right hemisphere. No stable change in the evoked response has been detected outside of the EEG paroxysm. CONCLUSIONS We postulate EEG interictal activity is able to induce impairment in processing auditory information and that this may play a role in the pathogenesis of language deficit in LKS.

Frontal Lobe Epilepsy Associated With Tuberous Sclerosis: Electroencephalographic-Magnetic Resonance Image Fusioning

We studied the topographic relationships between cortical and subcortical lesions shown on magnetic resonance images (MRI) and sources of epileptiform activity in a series of nine children with intractable epilepsy and tuberous sclerosis complex. Although video-electroencephalographic (EEG) monitoring was suggestive of a frontal seizure onset, interictal EEG was, in seven of nine cases, in the form of apparently bisynchronous discharges. In all cases, the use of a short time lag estimation procedure based on a nonlinear correlation function between surface recorded EEG signals allowed the detection of a lateralized onset of EEG paroxysmal activity. Furthermore, a computerized method based on a source localization EEG-MRI image fusioning procedure, has revealed a topographic concordance between well-defmed frontal cortical lesions shown on MRI and site of onset of paroxysmal discharges. Lennox-like EEG patterns frequently reported in children with tuberous sclerosis complex could be the result of the tendency of frontal tubers to induce secondary bilateral synchrony, with implications in the medical and eventually surgical management of the often drug-resistant associated seizures. (J Child Neurol 1998;13:33-38).

Computerized EEG Topography in Childhood Migraine Between and During Attacks

Topographic EEG mapping was performed in 58 migrainous children (mean age: 12.9 years; 39 without, 19 with aura) between attacks. Ten children were also recorded during an attack with visual aura. Between attacks there were no significant differences between migraineurs and age-matched controls. During visual aura a decrease in occipital alpha power contralateral to the affected hemifield was found in all patients. This was followed by a bilateral frontal increase in delta power, and, during the headache, by an increased delta activity in posterior-temporal and occipital electrode sites. The possible brain mechanisms underlying these EEG changes are discussed.

Tuberous sclerosis: relationships between topographic mapping of EEG, VEPs and MRI findings.

A group of 10 patients suffering from tuberous sclerosis (TS) and epilepsy was studied by means of topographic mapping of EEG and visual evoked potentials. The localizing ability of the technique was compared to the topography of hyperintense T2-dependent areas seen on magnetic resonance images (MRI). Data were collected from 19 electrodes, free from interictal EEG transients and artifacts, spectral analysis was performed using the FFT algorithm and color maps were produced by specialized equipment. Data were analyzed with respect to the presence of interhemispheric asymmetries and significant differences with age-matched normal controls. The topography of slow frequency components was the best clue for localization, with a concordance between imaging and spectral EEG data in 76% of the lesions detected by MRI. In 7 patients topographic mapping revealed spectral abnormalities in areas where MRI was not able to detect morphological lesions. These abnormalities were characterized by an increased delta (5 patients), theta (4 patients), or lowered ipsilateral alpha (1 patient) power. Although full agreement between imaging and electrophysiological data was not observed, we believe that in patients with TS the study of EEG rhythm activity can add valuable information to the visual inspection of the tracings.

Laterality of arm movement in full-term newborn

We have investigated 20 healthy full-term newborns between the 4th and the 6th day of life in standard conditions for laterality of arm movements, before and after introduction of a target. The durations of recording were: (a) 5 min continuously before target introduction; (b) five 1-min units during target presentation. The movements studied were extension, flexion, movement with semiflexed arm with hand half-open or open toward the midline of the body, and total movements. Each of these items were counted separately and the counts were compared within and between sides. Spontaneous movements showed no side preference whereas in the presence of the target, movements toward the midline (target directed movements) showed a significant right-hand preference.

The utilization of the Rorschach test in a case-controlled study

The Rorschach test was administered to 58 children of normal intelligence aged 7–14 years with a history of common migraine of at least 12 months and to a group of controls matched for age, sex, and IO. The Rorschach test was scored blindly. The migraine group was characterized by marked intellectual inhibition with poor school performance and low response rates; inhibition of psychomotor activity and aggressiveness, shown by content analysis and by the presence of kinesthetic shock; inhibition of affect (ratio M/sum C); ineffective use of mechanisms of defence against anxiety (F-); prevalence of phobic features and massive use of repression, indicated by the high rejection rate and shock at red colour. The differences from the controls were significant at the 0.01 level with regard to all items in the preadolescent age group and with regard to all items except kinesthetic shock in the migraine group as a whole. There was thus a definite difference between the migraine group and the controls, a difference that might depend on impairment of ego function and on recurrent experience of pain.

Pharmacotherapeutic and Non-Pharmacological Options for Refractory and Difficult-to-Treat Seizures

It is currently estimated that about 20%–30% of adults and 10%–40% of children diagnosed with epilepsy suffer from uncontrolled or poorly controlled seizures, despite optimal medical management. In addition to its huge economic costs, treatment-refractory epilepsy has a widespread impact on patients’ health-related quality of life. The present paper focuses on the concepts of refractory and difficult-to-treat seizures and their pharmacological management. Evidence on efficacy and tolerability of rational pharmacotherapy with antiepileptic drug combinations and of non-pharmacological treatment options such as epilepsy surgery, neurostimulation, metabolic treatment and herbal remedies is reviewed. The importance of early identification of the underlying etiology of the specific epilepsy syndrome is emphasized, to inform early prognosis and therapeutic strategies.