Age-related changes in EEG power spectra in infants during sevoflurane wash-out.

BACKGROUND: Few electroencephalography (EEG) data are available in anaesthetized infants. This study aimed to identify EEG characteristics that might warn of awakening (AW) from sevoflurane anaesthesia in infants. METHODS: Twenty intubated infants [aged 39-77 weeks post-menstrual age (PMA)] were studied after surgery during sevoflurane wash-out. EEG was recorded at the end of surgery and throughout emergence. Changes in EEG time and frequency domains were described. RESULTS: At the end of surgery, mean end-tidal sevoflurane concentration was 2.3% (range 1.5-3.5) before wash-out and reduced to 0.3% (0.1-0.6) when AW began. On AW, movement artifacts made signals difficult to interpret. Before awakening, most power was within frequencies ≤4 Hz, but trends over time were variable. Summated power in frequencies between 20 and 70 Hz was almost always <5 µV(2). During anaesthesia, there were two common power spectra: infants >52 weeks PMA had obvious summated power in the frequency range 5-20 Hz (P5-20 Hz) (mean 308, median 320, range 110-542 µV(2)), which decreased before awakening began [mean decrease 252 µV(2) (95% CI 153-351)], whereas younger infants had low P5-20 Hz throughout. P5-20 Hz during anaesthesia increased with age; power in this frequency band of ~100 µV(2) separated infants younger and older than 52 weeks PMA. CONCLUSIONS: During sevoflurane wash-out, decreasing P5-20 Hz might warn of impending AW in infants >3 months old, but not in younger infants.

Somatosensory discrimination: an intracranial event-related potential study of children with refractory epilepsy.

The objective of this study was to determine if a prefrontal somatosensory mismatch response (sMMR) could be recorded in response to deviations in duration of somatosensory stimuli. Intracranial somatosensory event-related potentials were recorded from temporal, parietal, and frontal lobe sites in 12 pediatric patients undergoing evaluation for epilepsy surgery. The stimuli were presented using an oddball paradigm and consisted of short vibratory bursts applied to hand digits 2 and 3. Early sMMRs, consisting of a negative and a positive component, were recorded over the postcentral gyrus and a later one, consisting of only a negative component, was recorded over the left middle frontal gyrus. The presence of an anterior sMMR suggests similar cortical processing to the auditory mismatch negativity (aMMN), with the posterior sMMR reflecting the neuronal processes involved in discriminating between stimuli and this is then followed by the anterior sMMR that may reflect processes involved in switching attention to these changes. The presence of both a prefrontal aMMN and sMMR may reflect activity with a multimodal network.

Impact of interictal epileptic activity on normal brain function in epileptic encephalopathy: an electroencephalography-functional magnetic resonance imaging study.

Using electroencephalography (EEG) in combination with functional magnetic resonance imaging (fMRI), we studied a 9.5-year-old girl who developed cognitive and behavioral regression in association with intense interictal bilaterally synchronous epileptic discharges (IBSEDs) both during the awake state and during sleep. During runs of IBSEDs, EEG-fMRI demonstrated deactivations in the lateral and medial frontoparietal cortices, posterior cingulate gyrus, and cerebellum together with focal relative activations in the right frontal, parietal, and temporal cortices. The deactivations probably reflect the repercussion of the interictal epileptic activity on normal brain function which might cause the neuropsychological regression by inducing repetitive interruptions of neurophysiological function resulting in a chronic state of specific psychomotor impairment. The relative activations could possibly indicate the source of epileptic activity rapidly spreading to other brain regions.

Effects of stimulus frequency and duration on somatosensory discrimination responses.

Somatosensory processing of duration and frequency changes was investigated using event-related potentials to vibrotactile stimuli. Intermittent vibration to the fingertips of either hand was presented using a two-stimulus odd-ball paradigm (deviant P = 0.10). One group (N = 12, 18-38 years) was presented with stimulus pairs of 20/70, 50/150 and 170/250 ms. A second group (N = 10, 19-34 years) was tested using frequency pairs of 200/70 Hz. A psychophysical study examined the subjects' ability to discriminate between different stimulus pairs. A clear negative shift in the response to the deviant stimulus was recorded with all the stimulus conditions used in both experiments. Both frequency changes and duration increments/decrements revealed an initial negativity in the subtraction waveform with a mean onset of 90-170 ms and a following positivity, both of which were dependent on the duration of the stimulus used. A significant decrease in the amplitude of both components was observed with the 170/250 ms pairing, coinciding with a positive correlation between individual discrimination performance and amplitude. These results support the existence of a somatosensory mismatch response with features similar to those of the aMMN and highlight the relevance of the somatosensory-specific positivity. Results from the duration experiment also resolve some of the discrepancies between previous studies.

Language reorganization in children with early-onset lesions of the left hemisphere: an fMRI study.

It is widely assumed that following extensive damage to the left hemisphere sustained in early childhood, language functions are likely to reorganize and develop in the right hemisphere, especially if the lesion affects the classical Broca's or Wernicke's language areas. In the present study, functional MRI (fMRI) was used to examine language lateralization in 10 children and adolescents with intractable epilepsy who sustained an early lesion in the left hemisphere. Lesions were adjacent to or within anterior language cortex in five patients, while they were remote from both Broca's and Wernicke's areas in the remainder. A lateralization index was calculated on the basis of the number of voxels activated in the left and right inferior frontal gyri when performing a covert verb generation task. Only two patients were right-handed, suggesting a high incidence of functional reorganization for motor control in the remaining patients. Five out of 10 showed bilateral or right language lateralization, but lateralization could not be inferred from the proximity of lesions to classical language areas on an individual basis. Lesions in or near Broca's area were not associated with inter-hemispheric language reorganization in four out of five cases, but with perilesional activation within the damaged left hemisphere. Paradoxically, lesions remote from the classical language areas were associated with non-left language lateralization in four out of five cases. Finally, handedness, age at onset of chronic seizures, and site of EEG abnormality also showed no obvious association with language lateralization. In conclusion, it is difficult to infer intra- versus inter-hemispheric language reorganization on the basis of clinical observations in the presence of early pathology to the left hemisphere.

Angelman syndrome reviewed from a neurophysiological perspective. The UBE3A-GABRB3 hypothesis.

Angelman syndrome is characterised by neurodevelopmental impairment (with or without epileptic seizures) associated with functional deficit of the UBE3A gene. Different mechanisms of UBE3A inactivation correlate with clinical phenotypes of varying severity. However, three distinctive, highly consistent electroencephalographic rhythmic patterns can be observed in almost all patients irrespective of genotype, clinical severity and the presence or severity of a seizure disorder. Pattern I consists of runs of high amplitude 2 - 3/s rhythmic activity predominating over the frontal regions. Pattern II consists of more diffuse runs of 4 - 6/s rhythmic activity. Pattern III consists of bursts or runs of high amplitude 3 - 5/s rhythmic activity, maximal over the occipital region, sometimes containing small spikes and facilitated by eye closure. We review the available neurophysiological evidence from human and animal studies in the light of recent molecular advances. Electroencephalographic features in both patients and various mouse models point to two separable categories: characteristic rhythmic patterns, which are not related to epilepsy, and less specific epilepsy-related discharge activity. These features are consistent with a model of cortical and thalamo-cortical dysfunction resulting from dysregulation of synaptic GABAergic neurotransmission by (1) deficient recruitment of functional GABA (A) receptors related to reduced UBE3A gene expression in all cases and (2) decreased amount of beta3 sub-unit in these receptors related to reduced GABRB3 gene expression in deletion cases.

Distinct multi-joint control strategies in spastic diplegia associated with prematurity or Angelman syndrome.

Spastic diplegia is commonly due to periventricular leucomalacia associated with premature birth. It is also a feature of Angelman syndrome (AS), a neurogenetic disorder with developmental delay, absent speech and mirthful behaviour. We studied the kinematics and kinetics of the squatting movement and associated electromyographic (EMG) activities in 20 children with spastic diplegia associated with periventricular leucomalacia (SDPL) or AS and 18 unimpaired children. While movement of normal subjects consisted of vertical translation of most body segments, the movement of SDPL children was operated around the fixed knee with backward shift of the hip, and AS children performed a forward flexion of the trunk over the thigh. Trunk stability was correlated with movement velocity in both pathological groups. In normal subjects, anticipatory EMG pattern consisted of silencing of hamstring muscle tonic activity prior to movement onset. This deactivation was not present in spastic diplegia. In SDPL, anticipatory overactivation of ankle joint actuators was recorded and tonic co-contraction persisted throughout the movement. In AS, rhythmic EMG bursting was seen during the movement. Shoulder, hip and knee trajectories in the sagittal plane showed marked within-group stereotypies in orientation, shape and length. The patterns in both pathological groups were therefore distinctive. We speculate that they reflect corticospinal impairment in SDPL and combined corticospinal and cerebellar dysfunction in AS.

Acute neurology and neurophysiology of haemolytic-uraemic syndrome.

Involvement of the central nervous system (CNS) is found in around 30% of children with haemolytic-uraemic syndrome (HUS). This complication is the single most common cause of mortality and also a major contributor to the morbidity associated with HUS. We reviewed 22 children with HUS and acute CNS involvement. Both global and focal derangements occurred, and in survivors, early regional EEG abnormalities-especially those in the occipital and temporal areas-were prognostically useful.

Cerebral dysplasias: reviewed from a neurophysiological perspective.

Improvements in neuroimaging techniques have highlighted the role of cerebral dysplasia in developmental disorders and in epilepsy. The current classification is founded on the presumed timing of the first insult as deduced from the imaging appearances. Although clinical neurophysiological findings are often non-specific, several unusual patterns have been reported in association with certain types of malformation. These include the high amplitude rhythmic activities of lissencephaly, and focal rhythmic spikes. In this general review, we describe the electroence-phalographic and evoked potential findings in a wide range of cerebral dysplasias, including our personal experience of rare conditions such as Ramer-Lin syndrome. We focus on their role in assessment and on potential insights into pathophysiology.

The reorganization of sensorimotor function in children after hemispherectomy. A functional MRI and somatosensory evoked potential study.

Children who have suffered extensive unilateral brain injury early in life may show a remarkable degree of residual sensorimotor function. It is generally believed that this reflects the high capacity of the immature brain for cerebral reorganization. In this study, we investigated 17 patients who had undergone hemispherectomy for relief from seizures; eight of the patients had congenital brain damage and nine had sustained their initial insult at the age of 1 year or older. Sensorimotor functions of the hand were investigated using functional MRI (fMRI) during a passive movement task, somatosensory evoked potentials (SEPs) arising from electrical and vibration stimulation, and behavioural tests including grip strength, double simultaneous stimulation and joint position sense. On fMRI, two of the eight patients studied with this technique (one with congenital damage and one with damage acquired at the age of 3 years) showed activation in the sensorimotor cortex of the remaining hemisphere with passive movement of the hemiplegic hand. The location of the ipsilateral brain activation was similar to that found on movement of the normal contralateral hand, although the latter was greater in spatial extent. In one of these patients, a greater role was demonstrated for the ipsilateral secondary sensorimotor area (compared with the ipsilateral primary sensorimotor area) for movement of the hemiplegic hand than for movement of the normal hand. Median nerve stimulation of the hemiplegic hand showed reproducible early-latency ipsilateral SEP components in the remaining sensorimotor cortex in 10 of the 17 patients (five with congenital and five with acquired disease). Five of the patients who demonstrated ipsilateral electrical SEPs also showed ipsilateral vibration SEPs (two with congenital and three with acquired disease). The behavioural tests revealed residual sensorimotor function in 14 of the patients; however, not all of the patients who exhibited ipsilateral SEP or fMRI responses had residual sensorimotor function in the hemiplegic hand. Ipsilateral sensorimotor responses were demonstrated both in patients with congenital disease and those with acquired disease, suggesting that factors additional to aetiology and age at injury may influence the degree of residual sensorimotor function and cerebral reorganization.

Insulin stimulation of muscle protein synthesis in obese Zucker rats is not via a rapamycin-sensitive pathway.

The obese Zucker rat is resistant to insulin for glucose disposal, but it is unknown whether this insulin resistance is accompanied by alterations of insulin-mediated muscle protein synthesis. We examined rates of muscle protein synthesis either with or without insulin in lean and obese Zucker rats with the use of a bilateral hindlimb preparation. Additional experiments examined insulin's effect on protein synthesis with or without rapamycin, an inhibitor of protein synthesis. Protein synthesis in red and white gastrocnemius was stimulated by insulin compared with control (no insulin) in obese (n = 10, P<0.05) but not in lean (n = 10, P>0.05) Zucker rats. In white gastrocnemius, rapamycin significantly reduced rates of protein synthesis compared with control in lean (n = 6) and obese (n = 6) rats; however, in red gastrocnemius, the attenuating effect of rapamycin occurred only in obese rats. The addition of insulin to rapamycin resulted in rates of synthesis that were similar to those for rapamycin alone for lean rats and to those for insulin alone (augmented) for obese rats in both tissues. Our results demonstrate that insulin enhances protein synthesis in muscle that is otherwise characterized as insulin resistant. Furthermore, rapamycin inhibits protein synthesis in muscle of obese Zucker rats; however, stimulation of protein synthesis by insulin is not via a rapamycin-sensitive pathway.

Language dysfunction in children with Rolandic epilepsy.

Rolandic epilepsy is regarded as the classic example of benign focal epilepsy. However, neuropsychological deficits have been noted in affected children. As Rolandic discharges are mainly distributed over the centrotemporal region, specific interference with language function might be suspected. Therefore, we conducted a standardized neuropsychological assessment in children with Rolandic epilepsy which covered all important aspects of language processing. We measured intelligence Quotient, verbal memory, auditory discrimination, vocabulary, grammar and literacy in 20 children with an active Rolandic focus. Information about performance at school was obtained from teachers by means of a questionnaire. Patients with Rolandic epilepsy failed five of the twelve standardized language tests significantly more often than the normative population and consequently showed impairment of the following functions: reading, spelling, auditory verbal learning, auditory discrimination with background noise and expressive grammar. Thirteen of the 20 children showed language dysfunction with difficulties in two or more of the twelve standardized language tests. In eight of these 13 children the Full Scale Intelligence Quotient was within average range, indicating a specific language deficit. Language dysfunction was closely associated with learning difficulties at school. This study documents a consistent pattern of language dysfunction in children with Rolandic epilepsy which suggests interictal dysfunction of perisylvian language areas.

Buccal absorption of midazolam: pharmacokinetics and EEG pharmacodynamics.

PURPOSE: To determine whether buccal/sublingual administration of midazolam (MDL) would lead to detectable venous concentrations and EEG changes in 10 healthy volunteers. METHODS: The study consisted of an open-label and a double-blind phases. Subjects held 10 mg MDL in 2 ml peppermint-flavored fluid or peppermint-flavored placebo in their mouth for 5 min and then spat it out. Cardiorespiratory and EEG monitoring was performed in all subjects. RESULTS: Venous MDL concentrations measured on 10 occasions from 5 to 600 min after administration showed a rapid increase for the first 20-30 min. However, changes in the 8- to 30-Hz frequencies identified by spectral analysis of the EEG showed changes in < or = 5-10 min in test but not in control subjects--more rapid than were expected from the venous absorption data. There were no significant adverse effects. CONCLUSIONS: Our data provide direct evidence of the speed of cerebral effect of a drug. Our results suggest that the buccal/sublingual route of administration should be tested in emergency treatment of seizures as an alternative to the rectal route, over which it has clear practical advantages.

Dacrystic seizures reconsidered.

Ictal lachrymation has not been reported in children as a main seizure manifestation. We report an infant with tuberous sclerosis who presented with seizures characterised by lachrymation without apparent emotional change associated with a left posterior temporal epileptic focus. We discuss the pathophysiological implications, and propose a clinically orientated classification of crying seizures.

Ictal cerebral perfusion related to EEG in drug resistant focal epilepsy of childhood.

OBJECTIVES: To evaluate the EEG changes during seizures in children with drug resistant focal epilepsy who demonstrate hypoperfusion at the "seizure focus" interictally, but no perfusion change during the seizure. METHODS: Ictal EEG findings of six children with focal epilepsy who demonstrated hypoperfusion on rCBF SPECT after an interictal injection of (99)Tc(m) HMPAO concordant with the seizure focus, but who did not demonstrate rCBF change after an ictal injection (group 1) were reviewed. These were contrasted with the EEG data of six children matched as closely as possible for age, type of epilepsy, and pathology who did show hyperperfusion at the seizure focus on ictal scan when compared with the interictal study (group 2). RESULTS: The children in group 1 showed slowing of the EEG at the time of the (99)Tc(m) HMPAO injection relative to that seen at the onset of the seizure. Those in group 2 showed rhythmic activity, or sharp waves, or both on EEG at the time of injection. This last change was also seen consistently when the EEG data of a further 13 children who also showed ictal hyperperfusion at the seizure focus were reviewed. CONCLUSION: Ictal rCBF does not invariably increase at the seizure focus in patients with drug resistant focal epilepsy.

High frequency non-invasive stimulation over the spine: Effects on mood and mechanical pain tolerance in normal subjects.

We investigated the effects of non-invasive high frequency (625Hz) stimulation over the spine on mechanical pain tolerance and subjective mood. Sixty healthy subjects were divided equally into three groups receiving either high intensity (250 V), low intensity (3-4 V) or sham electrical stimulation directly over the spinal cord for 30 minutes. Following high intensity stimulation, subjects felt significantly more elated, leisurely and less tense and, contrary to reports on patients with clinical pain, had lower mechanical pain tolerances. There were no correlations between changes in mood and changes in mechanical pain tolerances. These findings contrasted with the lack of any significant differences in mood or mechanical pain tolerances in a second study where 20 subjects received either high intensity or sham stimulation across the left shoulder joint. The results indicate that decreases in mechanical pain tolerance are independent of changes in mood following non-invasive high frequency, high intensity cutaneous stimulation but that both effects are dependent on that stimulation being applied over the spine.

Epileptic akinetic mutism: following temporal lobectomy for Rasmussen's syndrome.

A girl aged 9 years with Rasmussen's encephalitis previously treated by left temporal lobectomy suddenly developed prolonged attacks of extremely rapid respirations associated with poverty of body movements and greatly reduced facial movements with loss of speech. Her comprehension appeared intact and she responded to certain requests. Her eye gaze behaviour suggested a high degree of vigilance. The attacks would last from minutes to hours and were repeated up to a dozen times daily. In the context of the stress generated by the illness and other family problems the attacks had been mistaken for an hysterical elaboration. Their ictal nature was confirmed by EEG/video monitoring. Possible links with other developmental language disorders associated with epilepsy are discussed, including a model of autism.

A form of juvenile Batten disease with granular osmiophilic deposits.

The clinical, neurophysiological and pathological features of a patient who presented with the clinical features of juvenile Batten disease, yet who had storage of granular osmiophilic deposits (GROD) on ultrastructural examination of biopsy and postmortem tissues is described. The ultrastructural features are those usually found in the infantile form of Batten disease. The postmortem study showed marked neuronal storage of a lipofuscin-like material in an atrophic brain without loss of myelin. The cerebellum showed almost complete loss of Purkinje cells and loss of the granule cells. No accumulation of subunit c of mitochondrial ATP synthase was found. The clinical and neurophysiological findings are compared with those of the classical juvenile form and with those of the few reported cases of juvenile Batten disease with GROD. The importance of correct classification of patients with Batten disease and its impact on the molecular genetic studies is emphasised. The pathogenesis of this form of the disease is considered to be similar to that for infantile Batten disease.