Asymmetric POSTS associated with unilateral EEG abnormalities.

OBJECTIVE: Positive occipital sharp transient of the sleep (POSTS) are considered a normal variant of non-REM sleep EEG. We describe a small series of patients with asymmetric POSTS and ipsilateral abnormal EEG findings. METHODS: Over a period of 30 weeks, we prospectively observed five consecutive subjects with strictly unilateral POSTS associated with ispilateral electrographic abnormalities. They represent 0.4% of all EEG performed over the same time lapse (5/1130), including inpatients, outpatients and long-term monitoring. RESULTS: Four women and one boy suffering from epileptic seizures (aged 7-76 years old) had unilateral POSTS, occurring only on the right side, during light sleep. They also presented ipsilateral epileptiform abnormalities. CONCLUSION: The fact that POSTS were asymmetric and found only on the same side as the abnormalities raises the question whether these transients should still be considered physiological or could be interpreted at times as markers of underlying electrical abnormalities, pointing to an increased cortical excitability on the more active side. Although larger samples are needed to confirm our preliminary results, this case study questions the interpretation of POSTS as a uniformly normal variant.

Psychiatric comorbidity in patients evaluated for chronic epilepsy: a differential role of the right hemisphere?

INTRODUCTION: Psychiatric disorders are known to occur frequently in chronic epilepsy. The aim of this study is to investigate the prevalence of psychiatric comorbidity and its relationship to regional cerebral dysfunction in patients admitted to a tertiary epilepsy center for epilepsy surgery. METHODS: 217 patients were investigated. A presurgical workup was performed and allowed precise localization of the epileptogenic focus in 156 patients. Sixty-one patients had multifocal or generalized discharges. After 1-3 psychiatric interviews, a psychiatric diagnosis was made (DSM-IV classification). RESULTS: Psychiatric comorbidity was found in 85 patients (39%), more often in those with right or bilateral hemispheric dysfunction (74%, p = 0.04) with no difference between temporal or extratemporal foci location frequency. Additionally, patients with psychiatric disorders were less likely to undergo epilepsy surgery compared to 'epilepsy-only' patients (p = 0.003), despite similar good outcome in patients with and without psychiatric comorbidity. CONCLUSIONS: Right-sided or bilateral foci seem to represent a risk factor for psychiatric comorbidity in epilepsy, although we did not find any particular association between a psychiatric syndrome and focus localization. Recognition and treatment of psychiatric comorbidity is of major importance since its presence may interfere with patient's decision making for epilepsy surgery treatment.

Status epilepticus: an independent outcome predictor after cerebral anoxia.

BACKGROUND: Prognosis of status epilepticus (SE) depends on its cause, but there is uncertainty as to whether SE represents an independent outcome predictor for a given etiology. Cerebral anoxia is a relatively homogenous severe encephalopathy. Postanoxic SE is associated to a nearly 100% mortality in this setting; however, it is still unclear whether this is a severity marker of the underlying encephalopathy, or an independent factor influencing outcome. The goal of this study was to assess if postanoxic SE is independently associated with mortality after cerebral anoxia. METHODS: This was a retrospective observation of consecutive comatose survivors of cardiac arrest, including subjects treated with hypothermia. On the subgroup with EEG recordings in the first hospitalization days, univariate and multivariate analyses were applied to potential determinants of in-hospital mortality, and included the following variables: age, gender, type and length of cardiac arrest, occurrence of circulatory shock, presence of therapeutic hypothermia, and electrographic SE. RESULTS: Out of 166 postanoxic patients, 107 (64%) had an EEG (median latency from admission, 2 days); in this group, therapeutic hypothermia was administered in 59%. Death occurred in 71 (67%) patients. Postanoxic SE was associated with mortality regardless of type of acute cardiac rhythm and administration of hypothermic treatment. CONCLUSION: In this hospital-based cohort, postanoxic status epilepticus (SE) seems to be independently related to death in cardiac arrest survivors, suggesting that SE might determine a bad prognosis for a given etiology. Confirmation of these results in a prospective assessment is needed.

Post-ictal fever: a rare symptom of partial seizures.

Although fever may induce seizures, especially in children, its occurrence following epileptic spells has been rarely described, except from generalized convulsive status epilepticus. We present two patients suffering from focal seizures accompanied by episodes of post-ictal fever, and review similar reports in the literature of the last 40 years. Temperature changes following non-convulsive seizures might be induced by gene upregulation occurring in the hypothalamus, the nucleus tractus solitarius, or in other brain regions, producing a local inflammatory response. Direct propagation of electrical discharges seems less consistent with the timing of development of this symptom. Heterogeneity of reported clinical features argues against the assumption of a definite localizing or lateralizing value for post-ictal fever.

Continuous assessment of electrical epileptic activity in acute stroke.

OBJECTIVE: To determine the incidence and risk factors of electrical seizures and other electrical epileptic activity using continuous EEG (cEEG) in patients with acute stroke. METHODS: One hundred consecutive patients with acute stroke admitted to our stroke unit underwent cEEG using 10 electrodes. In addition to electrical seizures, repetitive focal sharp waves (RSHWs), repetitive focal spikes (RSPs), and periodic lateralized epileptic discharges (PLEDs) were recorded. RESULTS: In the 100 patients, cEEG was recorded for a mean duration of 17 hours 34 minutes (range 1 hour 12 minutes to 37 hours 10 minutes). Epileptic activity occurred in 17 patients and consisted of RSHWs in seven, RSPs in seven, and PLEDs in three. Electrical seizures occurred in two patients. On univariate Cox regression analysis, predictors for electrical epileptic activity were stroke severity (high score on the National Institutes of Health Stroke Scale) (hazard ratio [HR] 1.12; p = 0.002), cortical involvement (HR 5.71; p = 0.021), and thrombolysis (HR 3.27; p = 0.040). Age, sex, stroke type, use of EEG-modifying medication, and cardiovascular risk factors were not predictors of electrical epileptic activity. On multivariate analysis, stroke severity was the only independent predictor (HR 1.09; p = 0.016). CONCLUSION: In patients with acute stroke, electrical epileptic activity occurs more frequently than previously suspected.

[Status epilepticus and neuronal degeneration: of circuitries and vicious circles]. / Etat de mal épiteptique et neurodégénérescence: entre circuits et cercles vicieux.

The relationship between status epilepticus (SE) and neuronal degeneration is quite complex and difficult to investigate. Animal studies suggest that SE induces a progressive neuronal death; however, clinical observations on humans are less uniform: generalized SE may precede the development of hippocampal sclerosis, but other forms (such as simple-partial or complex-partial) seem less ominous. On the other side, SE can be encountered in many patients with neurodegenerative disorders, particularly those with severe forms. It is thus likely that SE represents a sign, rather than an aetiology, of clinical gravity. Therefore, while it is ancillary to treat rapidly any SE form, the therapeutic approach, especially the use of aggressive treatments, should be tailored according to the underlying medical conditions.

Levetiracetam in a broad population of patients with refractory epilepsy: interim results of the international SKATE trial.

OBJECTIVE: To prospectively assess the safety and efficacy of levetiracetam in patients with uncontrolled focal epilepsy, in a common practice-based setting. PATIENTS AND METHODS: In this phase IV, open-label, 16-week community-based study, adult patients with focal seizures initially received levetiracetam 1,000 mg/day. Throughout the study, the dose was adjusted in increments of 1,000 mg (maximum 3,000 mg/day) to achieve seizure control and maintain tolerability. The outcome parameters were the percentage reduction in partial and total seizure frequency per week from historical baseline, global evaluation scale (GES), and adverse events (AE). RESULTS: Seven hundred and thirty-one patients were included in this analysis and 84.4% completed the study. The median percent reduction in all seizures was 47.8%, and 49.3% for all partial seizures. The 50% responder rate was 49%, and the seizure-free rate was 17.2% for all partial seizures. Approximately 60% of patients showed moderate to marked improvement on the GES. The majority of AE were of mild to moderate severity; the most commonly reported being asthenia, somnolence, headache, and dizziness. CONCLUSION: Levetiracetam is both efficacious and safe as an add-on therapy in patients with refractory epilepsy treated by clinicians in their daily practice.

[Current epilepsy treatment in adults]. / Le traitement actuet des épitepsies chez l'adulte.

The prevalence of epilepsy is about 1%. Only two thirds of these patients respond satisfactorily to an antiepileptic drug (AED) treatment. New AED did not clearly improve this overall efficacy, but often show a better tolerability as compared to old AED. This may allow a more targeted choice, especially in some delicate clinical situations, such as for the treatment of women in childbearing age, or patients receiving other drugs with possible pharmacokinetic interactions. Invasive approaches should be considered early in the course of treatment-resistant epilepsy, and may offer a complete seizure remission in selected cases. On the background of recent acquisitions from the literature, the pros and cons of different treatment options are presented. This is followed by the discussion of some clinical relevant situations.

Automatic classification of HITS into artifacts or solid or gaseous emboli by a wavelet representation combined with dual-gate TCD.

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) can detect high-intensity transient signals (HITS) in the cerebral circulation. HITS may correspond to artifacts or solid or gaseous emboli. The aim of this study was to develop an offline automated Doppler system allowing the classification of HITS. METHODS: We studied 600 HITS in vivo, including 200 artifacts from normal subjects, 200 solid emboli from patients with symptomatic internal carotid artery stenosis, and 200 gaseous emboli in stroke patients with patent foramen ovale. The study was 2-fold, each part involving 300 HITS (100 of each type). The first 300 HITS (learning set) were used to construct an automated classification algorithm. The remaining 300 HITS (validation set) were used to check the validity of this algorithm. To classify HITS, we combined dual-gate TCD with a wavelet representation and compared it with the current "gold standard," the human experts. RESULTS: A combination of the peak frequency of HITS and the time delay makes it possible to separate artifacts from emboli. On the validation set, we achieved a sensitivity of 97%, a specificity of 98%, a positive predictive value (PPV) of 99%, and a negative predictive value (NPV) of 94%. To distinguish between solid and gaseous emboli, where positive refers now to the solid emboli, we used the peak frequency, the relative power, and the envelope symmetry of HITS. On the validation set, we achieved a sensitivity of 89%, a specificity of 86%, a conditional PPV of 89%, and a conditional NPV of 89%. CONCLUSIONS: An automated wavelet representation combined with dual-gate TCD can reliably reject artifacts from emboli. From a clinical standpoint, however, this approach has only a fair accuracy in differentiating between solid and gaseous emboli.

Uncommon ultrasound findings in traumatic extracranial vertebral artery dissection.

We report a case of internal carotid artery dissection (ICAD) associated with contralateral vertebral artery dissection (VAD). The interest of this case is to discuss an unusual Doppler pattern manifesting by a spectrum of an alternating vertebral artery flow suggesting a hemodynamic contribution from the contralateral vertebral artery (VA) and a clear depiction of both antegrade (red) and retrograde (blue) flow within the false and true lumen of the VAD by color Duplex flow imaging.

Midazolam premedication reduces propofol dose requirements for multiple anesthetic endpoints.

PURPOSE: This study investigates the interactions between midazolam premedication and propofol infusion induction of anesthesia for multiple anesthetic endpoints including: loss of verbal contact (LVC; hypnotic), dropping an infusion flex (DF; motor), loss of reaction to painful stimulation (LRP; antinociceptive) and attainment of electroencephalographic burst suppression (BUR; EEG). METHODS: In a double blind, controlled, randomized and prospective study, 24 ASA I-II patients received either midazolam 0.05 mg x kg(-1) (PM; n = 13) or saline placebo (PO; n = 11) i.v. as premedication. Twenty minutes later, anesthesia was induced by propofol infusion at 30 mg x kg(-1) x hr(-1). ED50, ED95 and group medians for times and doses were determined and compared at multiple anesthetic endpoints. RESULTS: At the hypnotic, motor and EEG endpoints, midazolam premedication significantly and similarly reduced propofol ED50 (reduction: 18%, 13% and 20% respectively; P <0.05 vs unpremedicated patients) and ED95 (reduction: 20%, 11% and 20% respectively; P <0.05 vs unpremedicated patients). For antinociception (LRP), dose reduction by premedication was greater for propofol ED95 (reduction: 41%; P <0.05 vs unpremedicated patients) than ED50 (reduction: 18%; P <0.05 vs unpremedicated patients). Hemodynamic values were similar in both groups at the various endpoints. CONCLUSIONS: Midazolam premedication 20 min prior to induction of anesthesia reduces the propofol doses necessary to attain the multiple anesthetic endpoints studied without affecting hemodynamics in this otherwise healthy population. The interaction differs for different anesthetic endpoints (e.g., antinociception vs hypnosis) and propofol doses (e.g., ED50 vs ED95).

The matching pursuit: a new method of characterizing microembolic signals?

Detection of clinically silent circulating microemboli within cerebral arteries by transcranial Doppler ultrasound (US) is now being widely investigated in the hope of identifying patients at increased risk for stroke. However, the widespread application of embolus detection is still limited in clinical practice because current transcranial Doppler systems have not the required sensitivity and specificity to analyze microembolic signals, particularly to distinguish between gaseous, or solid brain emboli and artefacts. In this work, we proposed to investigate the potential of a new approach for the analysis of microembolic signals via the so-called matching pursuit, which is closely related to wavelet transform and is not subject to the same limitations as the fast Fourier transform. Our preliminary results clearly indicate that matching pursuit is well suited to this task.

Visual stimulus-dependent changes in interhemispheric EEG coherence in humans.

We analyzed the coherence of electroencephalographic (EEG) signals recorded symmetrically from the two hemispheres, while subjects (n = 9) were viewing visual stimuli. Considering the many common features of the callosal connectivity in mammals, we expected that, as in our animal studies, interhemispheric coherence (ICoh) would increase only with bilateral iso-oriented gratings located close to the vertical meridian of the visual field, or extending across it. Indeed, a single grating that extended across the vertical meridian significantly increased the EEG ICoh in normal adult subjects. These ICoh responses were obtained from occipital and parietal derivations and were restricted to the gamma frequency band. They were detectable with different EEG references and were robust across and within subjects. Other unilateral and bilateral stimuli, including identical gratings that were effective in anesthetized animals, did not affect ICoh in humans. This fact suggests the existence of regulatory influences, possibly of a top-down kind, on the pattern of callosal activation in conscious human subjects. In addition to establishing the validity of EEG coherence analysis for assaying cortico-cortical connectivity, this study extends to the human brain the finding that visual stimuli cause interhemispheric synchronization, particularly in frequencies of the gamma band. It also indicates that the synchronization is carried out by cortico-cortical connection and suggests similarities in the organization of visual callosal connections in animals and in man.

The anterior mandibular positioning device for the treatment of obstructive sleep apnoea syndrome: experience with the Serenox.

Anterior mandibular positioning devices are seldom used at present in the treatment of obstructive sleep apnoea syndrome (OSAS). The aim of our study was to evaluate the efficiency, the side-effects and the patient compliance with one type of device made in Switzerland, the Serenox. This device is designed to keep the mouth closed with the mandible forward, avoiding the vibration of the soft palate. Between January 1996 and October 1997, 15 patients with OSAS were treated using a Serenox. One of them stopped using the device after 6 weeks due to the persistence of temporomandibular joint pain. Serenox was successful in 13 of the remaining 14 patients. The median pretreatment apnoea/hypopnoea index (AHI) of 36.25/h was decreased to 5.5/h after treatment (P < 0.002). Snoring and daytime sleepiness were notably reduced. The side-effects were frequent but mild and disappeared after a few weeks of adaptation. In conclusion, 87% (13/15) of the patients were treated successfully. Indications for the use of a mandibular positioning device include snoring, upper airway resistance syndrome and light to mild OSAS without severe obesity.

Midazolam premedication and thiopental induction of anaesthesia: interactions at multiple end-points.

We have studied the effects of midazolam premedication on multiple anaesthetic end-points (hypnotic, loss of verbal contact (LVC); motor, dropping an infusion flex or bag (DF); analgesic, loss of reaction to painful stimulation (LRP); and EEG, attainment of burst suppression (BUR)) during induction by slow thiopental infusion at a rate of 55 mg kg-1 h-1. Patients received midazolam 0.05 mg kg-1 i.v. (group TM, n = 12) or no midazolam (group T0, n = 13). ED50 and ED95 values and group medians for times and doses at the end-points were measured. Midazolam premedication reduced significantly thiopental ED50 and ED95 values at all end-points (exception for ED95 for BUR). Potentiation was greatest for the motor end-point (dropping the infusion bag (DF)) (ED95 +52%, ED50 +23%, median +39%), and smallest for painful stimulation (LRP) (median +18%; ED50 +13%). For LRP and DF, premedication was associated with significant, non-parallel increases in the slope of the thiopental dose-response curves, resulting in marked potency ratio changes from ED50 to ED95 (LRP +31%, DF +29%). There were no such increases for LVC or BUR. The interaction between midazolam and thiopental varied with the anaesthetic end-point and may also depend on the dose of thiopental. Our data suggest that the mechanism of interaction between midazolam premedication and thiopental was different for motor effects or analgesia (DF, LRP) compared with hypnotic effects or cortical depression (LVC, BUR), in agreement with the different central nervous system substrates underlying these distinct anaesthetic end-points.

[Recommendations for blood studies and clinical monitoring in early detection of valproate-associated liver failure. Results of a consensus conferences 9 May - 11 May 1997 in Berlin]. / Empfehlungen zu Blutuntersuchungen und klinischer Uberwachung zur Früherkennung des Valproat-assoziierten Leberversagens. Ergebnisse einer Konsensus-Konferenz vom 9.5.-11.5.1997 in Berlin.

Valproate is a frequently used antiepileptic drug. It is associated with rare but serious adverse effects like liver failure. The first symptom is impairment of the patient's well being. Isolated changes of standard laboratory liver parameters are not reliable early indicators. Thus, according to the knowledge of today, prophylactic blood screening cannot predict complications. On the contrary, clinical symptoms are the most relevant indicators of impending complications, eventually supported by laboratory findings. An abrupt withdrawal of valproate and administering carnitin in parallel can interrupt the otherwise fatal course of the complication and induce a subsequent recovery. At a Consensus Conference the current knowledge about early detection and therapy of the valproate-induced serious hepatotoxicity was discussed. The results regarding recommended laboratory screening, as well as diagnostic and therapeutic strategies are reported.

Childhood epilepsy with neuropsychological regression and continuous spike waves during sleep: epilepsy surgery in a young adult.

We describe the case of a man with a history of complex partial seizures and severe language, cognitive and behavioural regression during early childhood (3.5 years), who underwent epilepsy surgery at the age of 25 years. His early epilepsy had clinical and electroencephalogram features of the syndromes of epilepsy with continuous spike waves during sleep and acquired epileptic aphasia (Landau-Kleffner syndrome), which we considered initially to be of idiopathic origin. Seizures recurred at 19 years and presurgical investigations at 25 years showed a lateral frontal epileptic focus with spread to Broca's area and the frontal orbital regions. Histopathology revealed a focal cortical dysplasia, not visible on magnetic resonance imaging. The prolonged but reversible early regression and the residual neuropsychological disorders during adulthood were probably the result of an active left frontal epilepsy, which interfered with language and behaviour during development. Our findings raise the question of the role of focal cortical dysplasia as an aetiology in the syndromes of epilepsy with continuous spike waves during sleep and acquired epileptic aphasia.