Véronique Michel

Refractory status epilepticus: Electroconvulsive therapy as a possible therapeutic strategy

Refractory status epilepticus (SE) is a current daily therapeutic challenge. Electroconvulsive therapy (ECT), which is frequently used to treat psychiatric disorders, is known to raise the seizure threshold. As such, ECT could be of major interest in refractory SE. In this paper, we provide a brief overview of ECT in refractory SE. Although no placebo-controlled or open-label study has been published on the efficacy or safety of ECT in refractory SE, eight case reports have been identified. SE cessation was obtained in 80% of cases, and complete recovery was achieved in 27% of patients. Despite the heterogeneity of the ECT parameters used in these articles, we identified some common features that may be recommended for the use of ECT in refractory SE. ECT might be a viable therapeutic strategy for the most resistant and severe cases of SE, particularly after the failure of two inductions of anesthetic coma. This potential indication highlights the urgent need for clinical trials that assess the usefulness of ECT in refractory SE.

Application of U/Th and 40Ar/39Ar dating to Orgnac 3, a Late Acheulean and Early Middle Palaeolithic site in Ardèche, France.

Refined radio-isotopic dating techniques have been applied to Orgnac 3, a Late Acheulean and Early Middle Palaeolithic site in France. Evidence of Levallois core technology appeared in level 4b in the middle of the sequence, became predominant in the upper horizons, and was best represented in uppermost level 1, making the site one of the oldest examples of Levallois technology. In our dating study, fourteen speleothem samples from levels 7, 6 and 5b, were U/Th-dated. Four pure calcite samples from the speleothem PL1 (levels 5b, 6) yield ages between 265 ± 4 (PL1-3) and 312 ± 15 (PL1-6) thousand years ago (ka). Three samples from the top of a second stalagmite, PL2, yield dates ranging from 288 ± 10 ka (PL2-1) to 298 ± 17 ka (PL2-3). Three samples from the base of PL2 (level 7) yield much younger U/Th dates between 267 and 283 ka. These dates show that the speleothems PL1 and PL2 are contemporaneous and formed during marine isotope stage (MIS) 9 and MIS 8. Volcanic minerals in level 2, the upper sequence, were dated by the 40Ar/39Ar method, giving a weighted mean of 302.9 ± 2.5 ka (2σ) and an inverse isochron age of 302.9 ± 5.9 ka (2σ). Both 40Ar/39Ar dating of volcanic sanidines and U/Th dating of relatively pure and dense cave calcites are known to be well established. The first parallel application of the two geochronometers to Orgnac 3 yields generally consistent results, which point to the reliability of the two methods. The difference between their age results is discussed.

Benign nocturnal alternating hemiplegia of childhood: Two cases with positive evolution

Benign nocturnal alternating hemiplegia (BNAH) of childhood is distinct from the classic form of malignant alternating hemiplegia of childhood [1]. It is characterized by hemiplegic attacks occurring exclusively during sleep [2]. It can be misdiagnosed as migraine, nocturnal frontal lobe epilepsy, benign rolandic epilepsy, Panayiotopoulos syndrome, or sleep-related movement disorder [1-4]. Only nine patients have been described to date, with typically, a normal development [1,5-7]. In order to insist about the benignity of the affection, we report two cases: a new three-year-old boy suffering from BNAH and a patient already published to show positive evolution at fourteen years of age. BNAH is a rare disorder but may be underdiagnosed. Making an early diagnosis can help to describe to the parents the good prognosis without treatment.

New dating evidence of the early presence of hominins in Southern Europe

The first “Out of Africa” migrations represent a seminal event in the history of humankind. At the gates of Europe, the first appearance of Hominins is recorded in Georgia, 1.8 million years ago (Ma); however, the picture of migration across the continent remains incomplete. Vallonnet Cave (France) is a Lower Paleolithic prehistoric site with traces of hominin activities including lithic remains and cut-marks on mammal bones. Here, we apply the uranium-lead (U-Pb) methods to two flowstones to date the intervening archaeological levels. The U-Pb data, coupled with paleomagnetic constraints, provide an age range from 1.2 to 1.1 Ma. The results conclusively demonstrate that Vallonnet Cave is one of the oldest European prehistoric sites in France with early hominin occupations associated with an Epivillafranchian fauna. Combined with data from other archaeological sites, the new precise chronology suggests a widespread occupation the Northern Mediterranean to Southwestern Europe at ~1.2 Ma.

Conversion disorder and coexisting nonepileptic seizures in patients with refractory seizures

Nonepileptic seizures (NES) are commonly observed in patients with seizures resistant to antiepileptic drugs (AEDs). However, NES may be symptomatic of different diagnoses, in particular, conversion disorder (CD) and coexisting NES and epileptic seizures (CENES). We compared the clinical characteristics of these disorders in 219 patients with refractory seizures. The prevalence of NES was similar in children (11%) and adults (16%). In both groups, CENES represented the most frequent cause of NES (75%). In adults, CD was associated with a shorter duration of illness and normal neuroimaging and interictal EEG compared with the other groups. Patients with CD represented one-quarter of all patients with AED-resistant seizures with normal presentation during interictal investigations. In both children and adults with AED-resistant seizures, NES are frequently observed and are three times more likely to be CENES than CD.

Flexibility of bi- and triantennary glycans of the N-acetyllactosaminic type: A spin label study

Glycans appear to be recognition signals in several systems where interactions between glycoproteins and cellular receptors are involved [l-3]. The study of the conformation and mobility of such glycans may provide information about their biological role. The construction of molecular models of human serotransferrin glycans suggests that the two trisaccharide sequences: cY-Neu AC-(2 + 6)+Gal-(1 + 4)+GlcNac present in external positions have a helical configuration and, like ‘antennae’ are mobile [4]. To confirm these dynamics properties, the application of physical methods constitutes an interesting approach. Various investigators have carried out ESR studies of spinlabeled glycans of immunoglobulins [5-71 and membrane glycoproteins [&lo]. Attention was drawn in those studies to the fast motion of the probes. To study the dynamics properties of oligosaccharides in erythrocyte membranes, optical probes have been used [ 111: the fast motion was superimposed onto a slow motion which was attributed to cooperative movements of the oligosaccharide chains on the membrane surface [ 1 I]. Here, we describe the results obtained by spinlabeling sialic acid residues in two purified glycopeptides possessing biand triantennary glycans of known chemical structure. The ESRspectra have been recorded as a function of temperature in presence and absence of concanavalin A (con A). A fast motion of the probe is detected (7 < lo-’ s); however, analysis of the data obtained with doubly-labeled molecules, specifically

Long-term improvement of paroxysmal dystonic choreathetosis with acetazolamide

Sirs: Paroxysmal dyskinesias are a heterogeneous group of movement disorders characterized by recurrent brief episodes of abnormal involuntary movements [1–3] Among them, paroxysmal dystonic choreoathetosis (PDC) is associated with dystonic or choreic attacks unrelated to movement. It may occur spontaneously at rest without any triggering factors but attacks are frequently precipitated by caffeine or alcohol consumption, stress and fatigue. In contrast to paroxysmal kinesigenic choreathetosis (PKC), PDC attacks are more dystonic, usually last longer, and are less frequent with long attack-free intervals [3, 4]. Although most cases are familial, sporadic and secondary forms of PDC have been reported [4, 5]. We report a patient with a sporadic severe PDC which has been dramatically improved by acetazolamide over a period of three years. This 17-year-old boy who had a normal birth and no familial history developed his first symptoms at the age of 12. He presented recurrent episodes of left arm mild dystonia, along with attacks of paroxysmal non-kinesigenic dyskinesia involving the whole body. Short attacks (20 to 120 s) occurred 3 times a week to several times per day. They manifested as dystonia frequently beginning in the lower limbs, either on the left or right side of the body, spreading to the trunk and upper limbs and finally leading to falls. No aura or changes in consciousness were noted and no precipitating factors were reported. Clinical examination was normal. Occasionally, a mild left hand dystonic posture was observed when walking. Blood chemistry was normal. Wilson’s disease was excluded. Antibasal ganglia antibodies were negative on two examinations. Brain MRI, interictal electroencephalograms and iodobenzamide SPECT were normal. A videoencephalogram was performed for three consecutive days during which the patient exhibited several attacks without any epileptic activity on the EEG during attacks. Psychiatric evaluation was unremarkable. Owing to the analogy with paroxysmal ataxia (EA2) [6], screening was performed for CACNA1A gene. Screening by direct DNA sequence analysis of the 47 exons of the CACNA1A gene did not reveal any mutation. Analysis of triplets (involved in SCA6) was also normal. We also sought a mutation in the MR-1 gene encoding for the Myofrillogenesis Receptor 1 [7, 8]. Sequencing of the 10 exons of the transcript specifically expressed in the brain did not detect any mutation in the MR-1 gene. Tiapride chlorydrate, valproate sodium, carbamazepine and clonazepam at usual dosage were ineffective. Owing to similarities between attacks of PDC and periodic ataxia, acetazolamide (10 mg/ kg/day) was used off-label and the attacks resolved within two weeks. During the subsequent three years of follow up, the patient reported only two episodes of attacks during holidays. They clearly occurred when the patient neglected to take his treatment in the morning and they disappeared with acetazolamide, showing the strict correlation between relapse of attacks and drug intake. Treatment with acetazolamide was clinically well tolerated and regular examinationof blood samples was unremarkable. The clinical presentation of our patient points to a diagnosis of PDC because the paroxysmal dystonic attacks were not triggered by any particular movement, unlike in paroxysmal kinesigenic dyskinesia (PKD). Attacks were of short duration but a wide variability of symptoms is frequently noted in PDC, particularly concerning attack duration [2–4]. For example, one patient (P7) in the series of Bressman et al. [4] had attacks lasting only 10 sec to 5min, close to those observed in our patient. The dystonic nature of the attacks, the normal consciousness, and above all the absence of EEG V. Michel, MD AE D. Guehl, MD, PhD B. Bioulac, MD, PhD P. Burbaud, MD, PhD (&) Service de Neurophysiologie clinique Hopital Pellegrin Avenue Amelie-Rabat Leon 33076 Bordeaux, France Tel.: + 33/5 57 57 15 86 Fax: + 33/5 56 89 20 61 E-Mail: Pierre.Burbaud@umr5543. u-bordeaux2.fr

Clinical features of late-onset partial cryptogenic epilepsy: toward an idiopathic temporal epilepsy?

Adult-onset epilepsy is commonly thought to be secondary to a brain lesion. However, the etiology of adult-onset epilepsy remains unknown in approximately 25% of patients, despite progress in medical and diagnostic tools. In the present study, we investigated whether late-onset partial cryptogenic epilepsies could be subgrouped based on seizure semiology and clinical characteristics. A total of 41 patients with late-onset cryptogenic epilepsy were included, and the corresponding clinical and electrophysiological data were analyzed. The following three clinical subgroups were identified: 1) a group that fulfilled the diagnostic criteria of transient epileptic amnesia (TEA); 2) a group with late-onset cryptogenic epilepsies with a temporal seizure semiology; and 3) a cryptogenic extratemporal group, which was consistent with the categorization of cryptogenic epilepsies, i.e., epilepsies involving unknown lesions. The temporal group showed homogeneous clinical characteristics, especially a rapid evolution and a greater tendency toward generalization and pharmacoresistance compared with the other two groups. Transient epileptic amnesia was associated with a higher frequency of sleep disorders than either of the other groups. Our findings argue for the clinical identification of a subgroup of late-onset temporal epilepsy that might constitute an idiopathic form. The association between TEA and sleep disorders would suggest a possible pathophysiological role of sleep apnea syndromes in TEA.

Refractory Occipital Lobe Epilepsy Treated by Surgery in a Child with Chronic Encephalitis

An 11-year-old boy developed catastrophic occipital lobe epilepsy with progressive neurocognitive decline which led to surgical treatment. Pathological examination of the resected epileptic area showed chronic inflammatory changes. Surgery was followed by a subacute and regressive encephalopathy although the patient did not suffer further seizures. We suggest that this occipital lobe epilepsy was related to chronic nonprogressive encephalitis consistent with a variant of Rasmussen’s syndrome, and that the immune and/or inflammatory process was reactivated by surgery. This case indicates that there is no direct link between the epileptic and the encephalitic processes.

Datation ESR/U-Th combinée des restes fauniques du site moustérien de plein air de Beauvais (France)

Abstract Faunal remains from the Beauvais open site ‘La Justice’ (Oise) are the subject of an U-Th dating (disequilibrium of the uranium chain) and an ESR dating (electronic spin resonance). This study was performed in order to identify the chronological situation of the Middle Paleolithic levels of this site located in the north of France, supposedly aged stage 4 after stratigraphic correlations. U-Th ages of bones and dentine are between 20 and 200 ka and are scattered; however, the combined ESR/U-Th ages of rhinoceros dental enamels are homogeneous and indicate that the archaeological levels were deposited between 60 to 40 ka. This period corresponds to the end of the oxygen isotopic stage 4 to the beginning of stage 3.