Rhythmic movements in idiopathic REM sleep behavior disorder.

Reported are two cases of video-PSG captured head-rolling occurring, in the context of REM Sleep Behavior Disorder (RBD) episodes, in two patients affected with idiopathic RBD and without past personal or familiar history of Rhythmic Movement Disorder during sleep. It has been speculated that the activation of neuronal pathways which underlie REM-related loss of motor control in RBD, may involve the Central Pattern Generator neuronal networks leading to the induction of Rhythmic Movements during RBD episodes, thereby allowing the re-emergence, in pathological conditions in later life, of a motor behavior typically seen in the early stage of life.     

Synchronization between hippocampal theta waves and PGO waves during REM sleep.

We investigated the temporal relationship between hippocampal theta waves (referred to as 'theta waves') and ponto-geniculo-occipital (PGO) waves in cats. We measured the time intervals between an occurrence of a PGO wave and the prior and posterior adjacent positive peaks of the theta wave. The unimodal distributions of these intervals suggested a close temporal relationship between PGO and theta waves (i.e. synchronization). In addition, the period of a theta wave during which a PGO wave occurred was not statistically different from that without a PGO wave. This result suggests that the synchronization found here is characterized by phase-locking rather than phase-resetting. Common mechanisms are suggested to underlie the generation of PGO and theta waves.     

First true initial ictal SPECT in partial epilepsy verified by electroencephalography

Drug-resistant epilepsy can sometimes be treated by surgery. In these cases, an accurate identification of the epileptogenic area must be addressed before resection. Ictal SPECT is one of the presurgical evaluations that can be performed, but usually, the increase in the regional cerebral perfusion observed is produced by diffusion of ictal activity. Here we describe a patient studied with v-EEG and foramen ovale electrodes that suffered a seizure after intravenous infusion of etomidate. The sequence of etomidate administration, followed by radiotracer and seizure was good enough for us to suspect that a true initial ictal SPECT was observed. We have implemented a kinetic model with four compartments, previously described (Andersen 1989), in order to estimate the fraction of hydrophilic radiotracer in the brain during the pre-ictal and ictal periods. This model has shown that the fraction of hydrophilic radiotracer during the seizure into the brain would be between 18.9% and 42.3% of total infused. We show the first true initial ictal SPECT demonstrated by bioelectrical recordings of the brain activity, obtained by a correct succession of events and compatible with theoretical data obtained from the kinetic model.     

RTTBD‐like activity in association with hippocampal ictal discharges in patients with temporal lobe epilepsy

Aim. To determine clinical and intracranial EEG correlates of rhythmic temporal theta bursts of drowsiness (RTTBD) and assess its clinical significance in patients with temporal lobe epilepsy (TLE). Methods. A retrospective review of simultaneous scalp and intracranial video‐EEG recordings from 28 patients with TLE was evaluated for epilepsy surgery. Scalp RTTBD patterns were identified and their clinical and intracranial EEG correlates were then determined on video‐EEG recording using depth and subdural electrodes. Results. Thirty‐one RTTBD patterns on scalp EEG were observed in six (21%) of the 28 patients. Five (16%) of the RTTBD patterns occurred during wakefulness and 26 (84%) occurred during drowsiness and light sleep. The mean duration of RTTBD was 10 seconds (range: 3‐28 seconds). RTTDB consistently correlated with hippocampal ictal discharges and was time‐locked to the hippocampal seizures in which the ictal discharges evolved into rhythmic theta frequency (4‐7‐Hz) range. Ictal automatisms were observed during five (16%) RTTBD patterns, while cognitive impairment was observed in four (13%) of the 31 RTTBD patterns. Conclusion. Our findings show that scalp EEG correlates of hippocampal ictal discharges can resemble RTTBD and may be associated with ictal symptoms and cognitive impairment, indicating that RTTBD may rarely be an ictal EEG pattern in patients with TLE.     

Interictal hippocampal benzodiazepine receptors in temporal lobe epilepsy: comparison with coregistered hippocampal metabolism and volumetry

The significance of benzodiazepine receptor (BZR) concentration in comparison with hippocampal metabolism and volumetry was assessed in 14 patients diagnosed with temporal lobe epilepsy (TLE) without hippocampal signal change on T2-weighted magnetic resonance imaging (MRI) scans. Focus lateralization was achieved by clinical, electroencephalographic and neuropsychological examinations. Three-dimensional positron emission tomography (PET) and MRI scans were coregistered for determination of hippocampal 11C-flumazenil (FMZ) binding, normalized to average cortical values for glucose metabolism (rCMRglc) and volume. The hippocampi were individually outlined on T1-weighted MRI. Volumes of interest (VOI) were used for calculation of asymmetries between clinically affected and unaffected sides. Eleven out of 14 TLE patients presented a significant reduction in hippocampal volume. In nine of these 11 patients hippocampal FMZ binding and in seven cases hippocampal CMRglc was also reduced. In two patients without hippocampal volume asymmetry FMZ binding was markedly reduced in the mesial temporal lobe appropriately to the clinically diagnosed side. In our study volumetry is therefore the most sensitive tool for the detection of hippocampal abnormality in TLE. However, in cases without hippocampal atrophy the reduction of FMZ may indicate functional impairment of BZR before neuronal loss becomes evident. Our results emphasize the complementary nature of these tests in TLE patients.     

Theta-related gating cells in hippocampal formation: in vivo and in vitro study

In this study we extended our earlier in vitro findings concerning the discovery of a novel type of theta-related cells, which we have termed gating cells. There were two main objectives of our present investigations. The first was to determine the distribution of theta gating cells in the separated CA1 and CA3 generators in three different pharmacological conditions: (i) the presence of a cholinergic agonist-carbachol, (ii) the presence of carbachol and GABA(A) ergic antagonist-bicuculline, (iii) the presence of carbachol and GABA(B) ergic antagonist-2-hydroxysaclofen. The second objective of our studies was to verify our earlier in vitro findings and to demonstrate, for the first time, gating cells in intact hippocampus during the generation of Type II theta in urethane anaesthetized rats. Two hundred ninety-nine theta-related cells were isolated and recorded from in vivo and in vitro hippocampal formation. Twenty out of all 299 neurons (6.6%) were classified as gating cells. The neuron was classified as a gating cell if it met one of the following criteria: (i) the cell discharges occurred precisely in the beginning and at the end of each theta epoch (gating cell A); (ii) the cell began to discharge just before the transition from non-theta interval/LIA into the theta epoch (gating cell B); (iii) the cell began to discharge just after the transition from the theta epoch into non-theta interval/LIA (gating cell C). Our data demonstrates that the appearance of theta epochs and their length, as well as the appearance of non-theta states (in vivo recorded LIA or in vitro recorded intervals between theta epochs) and their length, may require the existence of a specific population of hippocampal neurons which we termed gating cells.     

Hippocampal rhythmic slow activity (RSA) during animal hypnosis in the rabbit

Hippocampal electrical activity has been studied in 12 unanaesthetized, unrestrained rabbits during hypnosis and spontaneous activity in the experimental cage, before and among hypnosis trials. Quantitative analyses showed that rhythmic slow activity (RSA) occurred during exploratory movements (mean frequency 7.2 Hz) and also during spontaneous immobility, but at a lower percentage and frequency (6.5 Hz). RSA was always present during the induction of hypnosis, but its frequency decreased and disappeared at the beginning of immobility, when it was replaced by a large amplitude irregular activity (LIA). During hypnosis RSA occurred in short periods, at low frequency (5.7 Hz). During the initial part of hypnosis, the lowest percentage of RSA was recorded. In the second and third part, RSA increased in number of episodes, total amount, duration of a single episode and mean frequency. RSA of higher frequency occurred at the end of hypnosis, preceding righting movements. The relationships between hippocampal RSA and animal hypnosis are discussed.     

Abnormal temporal lobe morphology in asymptomatic relatives of patients with hippocampal sclerosis: A replication study

We investigated gray and white matter morphology in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE+HS) and first‐degree asymptomatic relatives of patients with mTLE+HS. Using T1‐weighted magnetic resonance imaging (MRI), we sought to replicate previously reported findings of structural surface abnormalities of the anterior temporal lobe in asymptomatic relatives of patients with mTLE+HS in an independent cohort. We performed whole‐brain MRI in 19 patients with mTLE+HS, 14 first‐degree asymptomatic relatives of mTLE+HS patients, and 32 healthy control participants. Structural alterations in patients and relatives compared to controls were assessed using automated hippocampal volumetry and cortical surface–based morphometry. We replicated previously reported cortical surface area contractions in the ipsilateral anterior temporal lobe in both patients and relatives compared to healthy controls, with asymptomatic relatives showing similar but less extensive changes than patients. These findings suggest morphologic abnormality in asymptomatic relatives of mTLE+HS patients, suggesting an inherited brain structure endophenotype.     

Association between APOE polymorphisms and mesial temporal lobe epilepsy with hippocampal sclerosis.

To evaluate the hypothetical link between apolipoprotein E (APOE) polymorphisms and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and whether presence of APOE epsilon4 allele shortens the latent period between febrile seizures and epilepsy. A further interest is whether presence of APOE epsilon4 allele has an impact on severity of the disease. Forty-seven patients with MTLE-HS were compared with 62 controls. APOE polymorphisms were determined from lymphocytes by standard methods. Eight patients (17%) and 10 controls (16.1%) were demonstrated to have one APOE epsilon4 allele. There was not any statistically significant difference in APOE epsilon4 frequency between patients and controls (P > 0.05). There was not any difference statistically according to onset age of epilepsy and the presence of APOE epsilon4 allele within patient group. APOE epsilon4 polymorphisms did not influence the severity of epilepsy. APOE epsilon4 polymorphisms had no impact on outcome after surgery. Patients with bilateral memory deficits, bilateral hippocampal atrophy and with bilateral epileptiform interictal EEG transients, were independently compared with patients having unilateral features and there were not any statistically significant differences. This study has found no association between APOE epsilon4 polymorphisms and presentation of MTLE-HS in a group of Turkish patients.     

Distribution and analysis of hippocampal theta‐related cells in the pontine region of the urethane‐anesthetized rat

In the present study 99 cells were recorded in the pontine region of urethane‐anesthetized rats during: (1) the spontaneous occurrence of hippocampal formation (HPC) theta field activity; (2) sensory‐induced (tail pinch) theta field activity; and (3) large amplitude irregular field activity (LIA). Using the criteria of Colom and Bland (Brain Res 1997;422:277–286) for the classification of theta‐related cells, 58/99 cells (59%) were involved with changes in activity related to the occurrence of HPC theta field activity, 24/99 (24%) were non‐related, and 17/99 (17%) were related to the sensory input (tail pinch). All cells recorded discharged in a tonic, non‐rhythmic pattern in relation to the HPC field activity occurring during the three conditions. Of the 58 theta‐related cells, 52 (90%) were classified as tonic theta‐ON cells and 6 (10%) as tonic theta‐OFF cells. There were no clear regional differences in the distribution of cell types. Statistical analysis of the discharge rates of tonic theta‐ON cells during spontaneously occurring theta and tail pinch‐induced theta (tested on 48 cells) revealed that 22/48 (46 %) of these cells discharged at significantly higher rates during the faster theta field frequencies associated with tail pinches while 26/48 (54%) tonic theta‐ON cells did not change discharge rate between the spontaneously occurring theta and the tail pinch‐induced theta states. In addition, the discharges of 11/52 (21%) tonic theta‐ON cells exhibited weak to moderate correlations with the negative peak of HPC theta field activity recorded from the stratum moleculare of the dentate gyrus. Of the 17 cells related to the sensory stimulation (tail pinch), 12 (71%) cells increased discharge rate during the tail pinch and were classified as sensory activated, while 5 (29%) cells decreased discharge rate during the tail pinch and were classified as sensory inactivated. The results supported the following conclusions: (1) the main cells in the pontine region involved with changes in activity related to the occurrence of HPC theta field acitivity are tonic theta‐ON cells and tonic theta‐OFF cells; (2) a subpopulation of tonic theta‐ON cells coded the increasing intensity of activation of the ascending brainstem HPC synchronizing pathways by an increase in discharge rate; and (3) a smaller population of cells in the rostral pontine region appeared to be related to sensory stimulation, independent of theta‐related activity. Hippocampus 1999;9:288–302. © 1999 Wiley‐Liss, Inc.     

Rhythmic movement disorder (head banging) in an adult during rapid eye movement sleep.

Sleep-related rhythmic movements (head banging or body rocking) are extremely common in normal infants and young children, but less than 5% of children over the age of 5 years old exhibit these stereotyped motor behaviors. They characteristically occur during drowsiness or sleep onset rather than in deep sleep or rapid eye movement (REM) sleep. We present a 27-year-old man with typical rhythmic movement disorder that had persisted into adult life and was restricted to REM sleep. This man is the oldest subject with this presentation reported to date and highlights the importance of recognizing this nocturnal movement disorder when it does occur in adults.     

Foramen ovale electrodes can identify a focal seizure onset when surface EEG fails in mesial temporal lobe epilepsy

PURPOSE: We analyze a series of patients with mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) submitted to presurgical investigation with scalp sphenoidal, followed by foramen ovale electrodes (FO), and, when necessary, with depth temporal electrodes. We sought to evaluate the clinical utility of FO in patients with MTLE-HS. METHODS: We included patients who had phase I investigation with bitemporal independent seizures, nonlateralized ictal onsets, or ictal onset initiating in the side contralateral to the side of hippocampal sclerosis. Patients whose implanted FO failed to demonstrate an unambiguous unilateral ictal onset were later evaluated with depth hippocampal electrodes. RESULTS: Between May 1994 and December 2004, 64 patients met our inclusion criteria: 33 female (51.5%) and 31 male subjects (48.5%). The mean age at enrollment was 37.66+/-10.6 years (range, 12-56 years). The groups with nonlateralized surface ictal EEG onsets and contralateral EEG onsets had a greater chance of lateralization with FO when compared with the group with bilateral independent seizures on surface EEG (p<0.01). Foramen ovale electrodes lateralized the seizures in 60% of patients. Seventy percent of patients became seizure free after temporal lobectomy. Five patients were implanted with depth temporal electrodes after FO video-EEG monitoring. The depth-electrode EEG onsets confirmed the results of FO video-EEG monitoring in all patients, and the surgery was refused. CONCLUSIONS: In MTLE-HS, FO is a reliable method for lateralization of seizures that are not clearly recorded by surface EEGs.     

Rhythmic tongue movements during sleep: a peculiar parasomnia in Costello syndrome.

We describe a peculiar parasomnia observed in four Costello infants, characterized by periodic rhythmic movements of the tongue. Ten Costello patients (4 male; age range 9 months to 29 years) underwent 1 full-night laboratory-based video polysomnography. The four youngest patients (2 male and 2 female; age range 9-31 months) presented during sleep repeated stereotyped movements of the tongue, producing a sucking-like or licking-like movement, mostly during non-rapid eye movement (NREM) sleep. Rhythmic tongue movements in Costello syndrome show the features of an NREM sleep parasomnia. Tongue movements during sleep probably originate from brainstem structures and could be facilitated by an impaired control of the oropharyngeal and tongue muscles.     

Correlation study of optimized voxel-based morphometry and (1)H MRS in patients with mesial temporal lobe epilepsy and hippocampal sclerosis

Purpose:

To assess whether structural and metabolic brain abnormalities are correlated in MTLE/HS syndrome.

Methods:

Optimized voxel‐based morphometry (VBM) of gray matter concentration (GMC) and gray matter volume (GMV) and proton magnetic resonance spectroscopy measurements from both‐sided hippocampal and thalamic regions were performed in 20 MTLE/HS patients and 20 sex‐ and age‐matched healthy controls. The local GMC and GMV values were calculated in both the affected and unaffected hippocampi and ipsilateral and contralateral thalami in patients and healthy subjects, and these were compared. VBM variables and NAA, NAA/Cr and NAA/(Cr+Cho) values from the investigated brain regions were correlated.

Results:

(1) Analysis revealed significantly more extensive GMV reduction than GMC reduction in patients' affected hippocampus. In addition, significant GMV reduction was observed in the ipsilateral thalamus in MTLE/HS patients. (2) Significant decreases in all VBM and MRS variables were revealed in the affected hippocampus. Whilst practically normal GMC values were revealed in patients' both‐sided thalamic regions, a significant decrease in local GMV and metabolic measurements were found in the patients' ipsilateral thalamus. (3) Pearson's correlations between structural and metabolic abnormalities were significant for the ipsilateral thalamus only.

Conclusion:

Structural and metabolic abnormalities as detected by optimized voxel‐based morphometry and ¹H MRS in hippocampal and thalamic regions are only partially correlated in MTLE/HS patients. It seems therefore reasonable that both methods reflect different aspects of brain pathology, which, at least to some degree, might be independently ongoing. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.

     

ILAE Commission Report. Mesial temporal lobe epilepsy with hippocampal sclerosis

Experts discussed the definition, natural history, pathologic features, pathogenesis, electroclinical, neurophysiological, neuropsychological, structural and functional imaging findings, as well as surgical outcome in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). After a long-lasting consensus process the ILAE Commission Neurosurgery of epilepsy accepted the resulting conclusions as state-of-the art report on MTLE-HS. The majority of contributors considered MTLE-HS to represent a sufficient cluster of signs and symptoms to make up a syndromic diagnostic entity.     

Intracranial EEG in temporal lobe epilepsy: location of seizure onset relates to degree of hippocampal pathology

PURPOSE: To determine whether the specific location of electrographic seizure onset in the temporal lobe is related to hippocampal pathology in temporal lobe epilepsy (TLE). METHODS: Consecutive presurgical patients with scalp EEG-video evidence of TLE and no or mild hippocampal atrophy (HA) on magnetic resonance imaging (MRI) were prospectively studied by using depth and subdural strip electrode recordings to identify the site of the initial ictal discharge (IID). Thirty-four patients had either no or mild HA (HA- group). Four additional patients with moderate or marked HA (HA+ group) who required depth and strip electrodes served as a comparison group. Hippocampal pathology was assessed by MRI volumetrics and histopathologic grade of sclerosis (HS). RESULTS: Thirty-eight patients were investigated. In the HA- group, 10 patients had lobar ictal EEG onsets in the hippocampus (HF), medial paleocortex (MPC), and lateral neocortex (LNC); eight cases had regional IIDs in both HF and MPC; 12 persons had IIDs completely outside the HF; three cases lacked depth electrodes, and only one case (3%) had an IID confined to the HF. By contrast, three (75%) of four HA+ cases had IIDs confined to the HF (p = 0.002). Similarly, in 12 patients with low-grade HS, IIDs confined to the HF area were seen significantly less often than in six cases with high-grade HS (p = 0.025). CONCLUSIONS: In this study of a large number of patients with no to mild and a smaller group with moderate to marked HA and HS, the location of seizure onset in the temporal lobe was related to the degree of hippocampal pathology. Absence of HA and low-grade HS was each associated with IIDs in both the hippocampus and medial (with or without lateral) temporal cortex, or only the MPC or LNC. Marked HA and high-grade HS both were associated with IIDs restricted to the HF.     

Marked accumulation of oligodendroglia‐like cells in temporal lobe epilepsy with amygdala enlargement and hippocampal sclerosis

Although an increasing number of cases of temporal lobe epilepsy (TLE) with ipsilateral amygdala enlargement (AE) have been reported, there are few pathological reports, and no clear consensus has been established. Oligodendroglia or oligodendroglia‐like cells (OLCs) have recently attracted attention in epilepsy studies. Here, we report the clinical and pathological findings of a 40‐year‐old male TLE patient with AE and hippocampal sclerosis, in whom histopathological study demonstrated remarkable clustering of OLCs around the uncus. The patient began to have refractory seizures at the age of 14, and preoperative MRI revealed left amygdala enlargement and left hippocampal atrophy. Other examinations were consistent with left mesial temporal epileptogenicity. He underwent surgical resection and achieved seizure freedom. Histopathological study of the amygdala showed swollen neurons with relatively large bodies and thick neurites, accompanied by vacuolar degeneration in the background. Additionally, there were marked clusters of OLCs with round nuclei and densely stained chromatin around the uncus. The OLCs were Olig2‐positive. In the hippocampus, severe cell loss in CA1 and granule cell dispersion in the dentate gyrus were found. These findings may provide some insights for further pathological investigations of TLE with non‐neoplastic AE.