Effects of amygdala-hippocampal stimulation on interictal epileptic discharges.

Deep brain stimulation (DBS) of different nuclei is being evaluated as a treatment for epilepsy. While encouraging results have been reported, the effects of changes in stimulation parameters have been poorly studied. Here the effects of changes of pulse waveform in high frequency DBS (130 Hz) of the amygdala-hippocampal complex (AH) are presented. These effects were studied on interictal epileptic discharge rates (IEDRs). AH-DBS was implemented with biphasic versus pseudo monophasic charge balanced pulses, in two groups of patients: six with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) and six with non lesional (NLES) temporal epilepsy. In patients with HS, IEDRs were significantly reduced with AH-DBS applied with biphasic pulses in comparison with monophasic pulse. IEDRs were significantly reduced in only two patients with NLES independently to stimulus waveform. Comparison to long-term seizure outcome suggests that IEDRs could be used as a neurophysiological marker of chronic AH-DBS and they suggest that the waveform of the electrical stimuli can play a major role in DBS. We concluded that biphasic stimuli are more efficient than pseudo monophasic pulses in AH-DBS in patients with HS. In patients with NLES epilepsy, other parameters relevant for efficacy of DBS remain to be determined.

[Generics of antiepileptic drugs]. / Génériques des médicaments antiépileptiques.

Generic substitution of antiepileptic drugs (EAD) have limited use because epilepsy is a chronic disease, seizure recurrence has an important impact of the quality of life and the potential risk of accidents. EADs have a narrow therapeutic window, non negligible side effects and complex interactions. Bioavailability of generic EADs, tested in healthy men during a limited period of time must be within the 90% IC, in which means that serum levels can range from 80% to 125% of the original drug. A slight drop in serum level could increase the risk of seizure recurrence, as indicated by several publications. Although no formal studies regarding cost effectiveness and the rate of seizure recurrence is available yet, the prevailing consensus recommends not to replace an original antiepileptic drug by a generic, due to the harmful risk of seizure recurrence.

[Mental disorders and epilepsies]. / Troubles psychiques et épilepsies.

Mental disorders in patients having difficulties to treat their epilepsy are without a doubt more frequent than those presented by patients with controlled epilepsies or within a general population. These problems are especially affective disorders; clinical presentations of these troubles are often particular and difficult to classify through the current admitted classification guidelines. We speak generally about an interictal dysphoric disorder. The relationship between observed troubles in seizures is in some cases very particular: postictal depressions and psychosis are very peculiar disorders, self limited, difficult to detect and to treat. Some considerations are made about certain topics related to severe epilepsies: suicide, pseudo seizures and therapeutic attitude.

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.

[Cervicogenic headaches]. / Les céphalées cervicogéniques.

Cervicogenic headaches are a relatively new nosological entity. The diagnostic criteria are still under discussion. They are rare: the diagnostic is based on anamnestic and clinical considerations. Rx investigation is mandatory. The aetiology is multifactorial. In case of cervical trauma, the relationship with the primary peripheral lesion must be carefully discussed. The actual opinion from the neurophysiological point of view is based on the hypothesis of "central hypersensitivity". This progressive dysfunction is probably modulated by genetic characteristics: the mechanism is triggered by the initial peripheral nociceptive input. In chronic situations, psychosocial factors are important. The treatment must be considered individually. It is based on a pharmacological approach and, in selected cases, includes anaesthetic block.

[The senologist surgeon]. / Il chirurgo senologo.

Senology is going to be an independent branch, but resistances to the acknowledgement of the senologist as a devoted professional are still under way. Nevertheless, in the last 20 years an irreversible educational training was traced out. The senologist is not only the surgeon who operates on the breast: he is also a clinician, a researcher and a philosopher. Restricting the senologist's role to that of a knife-user is by far reductive, as this does not put in its true light his huge knowledge: senology is first of all a cultural item. Europe is going to set up independent Breast Units because this is the only way to offer excellent services, whose final result will be the reduction of mortality and the improvement of quality of life.

Comparative single-dose pharmacokinetics of clonazepam following intravenous, intramuscular and oral administration to healthy volunteers.

The objective was to assess the single-dose pharmacokinetics of clonazepam following i.m., p.o. and i.v. administration. In an open-label, three-way crossover study, 12 healthy volunteers were randomized to receive a single dose of 2 mg clonazepam either by the i.m., p.o. or i.v. route. Serial blood samples were collected up to 120 h after drug administration. Plasma concentrations of clonazepam were determined by electron-capture gas-liquid chromatography. The absorption rates of clonazepam after i.m. and p.o. administration of clonazepam were significantly different from each other, as reflected by the respective mean values of maximum plasma concentration (C(max) 11.0 vs. 14.9 ng.ml(-1)) and time to reach maximum concentration (t(max) 3.1 vs. 1.7 h). Secondary plasma peaks of clonazepam were observed in 9 volunteers after i.m. injection (C(max) 9.9 ng.ml(-1); t(max) 10.4 h). A comparison of the area under the plasma concentration-time curves (AUC) shows that the i.m. route is equivalent to the oral route (AUC(0- infinity ) 620 vs. 561 ng.h.ml(-1)). Clonazepam was almost completely absorbed after i.m. and p.o. administration, as shown by the mean absolute bioavailability of 93 and 90%, respectively. No significant differences existed between the elimination half-lives (i.v. 38.0 h; i.m. 43.6 h; p.o. 39.0 h). The average clearance and volume of distribution (V(Z)) were 55 ml.min(-1) and 180 liters, respectively. In conclusion, the observed differences in C(max) and t(max) after i.m. and p.o. administration were consistent with a slower absorption rate of clonazepam after i.m. injection. The systemic exposure to clonazepam was not affected by the route of extravascular administration. Statistical evaluation of these kinetic data showed differences in the absorption rate, so that clonazepam given by the i.m. route is not bioequivalent to the oral route. On the basis of the results of this study, we would recommend the same i.m. and p.o. dose in epileptic patients, but therapeutic response would be expected to be less predictable and to occur later in the case of i.m. administration.

[Outcome in very severe stroke]. / Evolution des accidents cérébro-vasculaires très sévères.

Functional outcome after stroke with severe disability (Barthel Index<60 points) was analyzed retrospectively in one hundred patients, including seventy-three with nonhemorrhagic stroke and twenty-seven with hemorrhagic stroke admitted to our neurorehabilitation center between 1986 and 2000. Neurological deficits and functional disabilities were assessed with the Barthel Index at admission to rehabilitation and after the rehabilitation program in survivors. The rehabilitation therapy was based on the Bobath concept. Patients were not discharged until neurological and functional stability had been reached. There was no difference for age, length of stay, Barthel Index scores at admission and discharged between the groups. Gain in the Barthel Index scores between admission and discharge (p=0.005) resulted from more efficiency in the group with hemorrhagic stroke. These patients appeared to exhibit better functional gain at discharge from rehabilitation than nonhemorrhagic patients. This observation points out that long-term outcome is also better for patients who experience hemorrhagic stroke.

[Clinical utilization of new anti-epileptic agents]. / Que faire des nouveaux anti-épileptiques?

Since the beginning of the 1990's, a dozen of new anti-epileptic drugs have been on the market or will be soon. This article reviews the daily clinical utilisation of new anti-epileptic drugs. It considers, without being complete, the current opinions and tendencies. The new anti-epileptic substances are generally as efficient as conventional medications. However, they are better tolerated and are more easily used in combination with conventional anti-epileptic drugs. Polytherapy is certainly the form of treatment, which is used in the most cases of resistant epilepsies. The surgical treatment can be used in only a very limited number of cases. The objective of treatment is the complete control of seizures, with minimum secondary effects. Though this objective is rarely reached, the NAE significantly improves the quality of life of patients suffering from severe epilepsy. The utilisation of NAE is not without risk. Increase in the frequency and severity of seizures may occur; we should remember that severe adverse effects appeared in the post-marketing period of the use of Vigabatrine and Felbamate. Therefore, we must remain vigilant in the clinical use of the anti-epileptic drugs.

[Minor cranio-cervical injuries, cerebral malformations and chronic headaches]. / Traumatisme cranio-cervical mineur, malformation cérébrale et céphalées chroniques.

We have presented two cases of chronic disabling exertional headaches following a minor head trauma. MRI studies of the cranio-cervical junction showed Chiari Type I malformation, without bony occipito-cervical dysplasia. Headaches after a mild trauma are a common finding. The exertional character of the headache can lead the clinician to his diagnosis in cases involving long-term complaints.

[Management of patients with simple cervical distortions]. / Prise en charge des patients avec entorses cervicales simples.

Common distortion of the cervical spine without evidence of neurological or osteoligamentary damage is a frequent consequence of indirect head and neck trauma. The mechanism of the injury (called "whiplash", "coup de lapin", or "Schleudertrauma") does not imply direct trauma to the head or neck. In the acute phase, common distortion of the cervical spine requires treatment. Rapid management may avoid or considerably reduce the chronic pain syndrome with the characteristic chronic tension-like headache. The chronic pain and the numerous associated functional disorders are not well understood: certain factors favour central and peripheral dysfunction and others emphasize the importance of extra-trauma phenomena. In our opinion, extra-trauma phenomena would explain the invalidating nature of pain in a small number of patients. Management of these chronic patients requires a multidisciplinary approach aimed at helping the patient overcome the inconveniences of this condition.

Reduction of plasma alanine aminotransferase during vigabatrin treatment.

In 9 drug-resistant patients with partial seizures treated with vigabatrin, gamma-vinyl GABA (VGB), alanine aminotransaminase (ALAT) activity in plasma was significantly reduced. Comparison of in vitro with in vivo measurements led us to conclude that this reduction is mainly an in vivo phenomenon, perhaps due to cross-enzyme inhibition. The assessment of two biological variables linked with ALAT, glucose and alanine levels under fasting conditions, failed to show any significant metabolic alterations. VGB is an effective drug for partial epilepsy. Our observations do not suggest that reduced ALAT activity is of clinical concern.

[Characteristics of chronic headaches after whiplash injury]. / Caractéristiques des céphalées chroniques après entorse cervicale.

OBJECTIVES: The aim of this study was to identify the characteristics of post-traumatic headache after whiplash injury in order to obtain some indications as to the pathogenesis of this particularly frequent clinical entity. METHODS: A retrospective study of 63 patients who had suffered whiplash injury and who had persistent chronic pain was conducted. RESULTS: Forty-seven patients complained of headache and pain in the cervical spine and 16 of pain in the cervical spine alone. Among the patients with headache 74% complained of tension-like pain, while only about 10% had identifiable post-trauma migraine headache with or without aura. Current neurophysiological hypotheses of central dysfunction due to neurochemical disorders induced by the initial nociceptive stimuli, frequently found in the general population, would not explain the disabling characteristics observed in these patients with chronic pain. CONCLUSION: A multifactorial pathogenesis of post-traumatic chronic headache should be entertained, suggesting that not only trauma but also extra-trauma factors unrelated to whiplash would be involved.

[Severe epilepsy and mental handicap in young adults. Epidemiological survey]. / Epilepsies sévères et handicap mental chez le jeune adulte. Enquête épidémiologique.

This study of prevalence is based in a population of 34,577 people aged from 15 to 19 resident in the canton of Vaud (Switzerland) and on the Swiss Federal Disability Insurance files (AI, AVS, IV), a compulsory insurance for all young residents. The study had two aims: firstly, to evaluate the necessary number of institutional beds for people needing multidisciplinary management because of medical, social and educational problems related to severe epilepsy, secondly, to form an idea of the number of epileptic patients needing to be considered for surgical treatment of epilepsy. In fact, we collected only 12 cases requiring multidisciplinary institutional assessment and management due to refractory epilepsy associated with mild or moderate mental handicap. Clinicians dealing with epileptic patients believe that people for whom surgical treatment needs to be considered are rare: the study confirms this rarity. We found this indication to be clearly legitimate in only 7 patients (less than 10% of all epileptic patients).

[Chronic pain sequelae after trauma of the cervical spine]. / Séquelles douloureuses chroniques des traumatismes de la colonne cervicale.

This presentation summarises the opinions concerning chronic pain after mild cervical trauma without neurological and radiological findings. Clinicians are often surprised by the disabling character of the pain, despite the lack of severe lesions. The initial lesions lead in some cases to chronic headache having different features associated with cervical pain, but in our opinion this pain does not have a disabling nature. When the disabling character is present, we postulated that it is associated with other psychological, social and professional factors. In fact, the pathogenesis of this chronic disorder is multifactorial. Its treatment doesn't lead to healing but to better management of patient life with chronic pain.

Haemmaccel, a key for lung preservation?

Several and different solutions have been used for lung preservation but, at present, fluids and solutions are quite alike. In the last years extracellular type solutions have been progressively tested in experimental researches and have shown a better protection vs intracellular one. In this research we have studied the effect of a low-potassium solution normally used as plasma expander (Haemmaccel, HM) on isolated foetal human fibroblasts (WI-38). HM has been compared with Belzer solution (UWS) after 16 hrs incubation at 10 degrees C and low-potassium solutions with dextran 2% and 5% after 6 hrs and 16 hrs incubation at 10 degrees C. Wi-38 cells have been seeded at the density of 9x10(4)/cm2 onto plastic well plates. Cellular viability was measuring using the rate of protein synthesis through the incorporation of 3H leucine in growth medium during a 1 hr incubation at 37 degrees C. The results were expressed as nmol 3 H leu/mg of proteins/minute and presented as means +/- SD; the comparison has been performed by the one way variance analysis test. After 16 hrs incubation at 10 degrees C HM preserves WI-38 cells significantly better than UWS. Comparing HM with LPD 2% and 5% a significant difference both at 6 hrs and at 16 hrs was observed. Our preliminary in vitro results confirm that low-potassium solutions are less toxic on isolated lung cells than intracellular one. Polygelin contained in HM could be considered a suitable colloidal substance that determine a better preservation if compared with Low-Potassium Dextran solutions.

Influence of lamotrigine addition on computerized background EEG parameters in severe epileptogenic encephalopathies.

In 12 adults with typical Lennox-Gastaut syndrome and partial epilepsies with secondary bilateral synchrony unsatisfactorily controlled by current antiepileptic drugs, the following computerized background EEG parameters were studied before and during beneficial antiepileptic effect of lamotrigine addition: absolute and relative spectral power density; alpha/theta index; dominant frequency of occipital alpha, theta and delta bands. The only significant influence of lamotrigine addition was a moderate decrease of the median and mean absolute delta power (p < 0.01). We concluded there was a poor influence of therapeutic doses of lamotrigine on the background diffuse slow dysrhythmias characteristic to severe early encephalopathies which engender both severe secondary epilepsies and different degrees of mental handicap.

[Management of chronic neurologic patients: apropos of patients with severe cerebrovascular involvement]. / Prise en charge des malades neurologiques chroniques: à propos de malades avec atteintes cérébro-vasculaires sévères.

We present clinical date and follow up in a rehabilitation unit with a multidisciplinary team for twenty two old patients with severe cerebrovascular disease. The patients were fully examined in the "Service de neurologie de Lausanne". New cerebral vascular accidents occurred in three patients. The other patients improved in functional status evaluated by the Barthel-Index in spite of no significant changes in neurological and neuropsychological status.