First line management of prolonged convulsive seizures in children and adults: good practice points

Over the past decades, it has become clear that the most efficient way to prevent status epilepticus is to stop the seizure as fast as possible, and early treatment of prolonged convulsive seizures has become an integral part of the overall treatment strategy in epilepsy. Benzodiazepines are the first choice drugs to be used as emergency medication. This treatment in the early phases of a seizure often implies a ‘pre-medical’ setting before intervention of medically trained persons. In this paper, we propose “good practice points” for first line management of prolonged convulsive seizures in children and adults in a ‘pre-medical’ setting.     

Evidence for a microglial reaction within the vestibular and cochlear nuclei following inner ear lesion in the rat.

Following unilateral inner ear lesion, astrocytes undergo hypertrophy in the deafferented vestibular and cochlear nuclei as shown by an increase in the level of glial fibrillary acid. The present study extends our understanding of vestibular and cochlear system plasticity by examining microglial changes in these deafferented nuclei. The microglial reaction was studied 1, 2, 4, 8, 14, 21, 28 and 42 days following the lesion with a monoclonal OX-42 antibody and lectins (Griffonia simplicifolia, B4 isolectin) labelled with horseradish peroxidase or fluorescein. The deafferented nuclei were also examined for apoptotic cells by terminal transferase-mediated nick end labelling of nuclear DNA fragments. In control and sham-operated rats, the distribution of the resting microglial cells was uniform in both the vestibular and cochlear nuclei. In the deafferented vestibular complex, the microglial cells increased in number, became hypertrophied and were distributed in the medial, lateral, superior and inferior vestibular nuclei. Reactive microglial cells were also detected in the ipsilateral cochlear nuclei. Some of the immunostained cells were hypertrophic whereas others presented an ameboid morphology with few short and stout processes. The microglial reaction was confined to the antero- and posteroventral cochlear nuclei. Finally, reactive microglia was also observed in the prepositus hypoglossi ipsilateral to the lesion. The microglial reactions within the prepositus hypoglossi, the vestibular and the cochlear nuclei were detectable as early as one day after the lesion and persisted several weeks in both the vestibular and cochlear nuclei. Apoptotic cells were not detected in the vestibular nuclei at any stage following the lesion. In contrast, terminal deoxynucleotidyl transferase-mediated digoxygenin-11-dUTP nick end labelling-positive cells were first detected in the deafferented cochlear nuclei on the 3rd day following the lesion. They reached an apparent maximum by day 8 and then declined until day 24. Double labelling experiments demonstrate that these cochlear terminal deoxynucleotidyl transferase-mediated digoxygenin-11-dUTP nick end labelling-positive cells were also lectin-positive suggesting that reactive cochlear lectin-positive microglia cells were eliminated by a programmed cell death. Our results establish the two experimental models as reliable tools to understand the role of microglia in adult brain plasticity. The cochlear microglial reaction was probably induced by the degeneration of the acoustic nerve which follows the acoustic ganglion destruction. Interestingly, the same reasoning cannot apply to the vestibular microglial reaction following unilateral labyrinthectomy: the vestibular ganglion was spared and the primary vestibular neurons did not degenerate, at least during the first week following the lesion.     

Saccular dysfunction in Meniere's disease

OBJECTIVE: The aim of this study was to assess any dysfunction of the sacculus in patients with unilateral Meniere's disease by monitoring the vestibular evoked myogenic potentials (VEMPs) evoked by high level clicks on the Stemomastoid muscles (SCMs). STUDY DESIGN: The study was a retrospective analysis. SETTING: The study was performed in the E.N.T. department of the Lariboisière Hospital. PATIENTS: Fifty-nine patients aged 18 to 74 years with well-established unilateral Meniere's disease were included in the study. INTERVENTIONS: Loud monaural clicks were delivered unilaterally, and the VEMPs were recorded with skin electrodes on the ipsilateral SCM. All the patients were also subjected to a pure tone audiometric test and bithermal caloric testing. The postural performances of 39 patients were analyzed using the Equitest. MAIN OUTCOME MEASURE: VEMP results were the main outcome measure. RESULTS: The saccular response was absent on the affected side in 54% of the patients with Meniere's disease. This absence was correlated with the degree of low frequency hearing loss but not with canal paresis. Finally, nonfalling patients with saccular dysfunction had a significantly poorer postural performance than those without such dysfunction in the condition 5. CONCLUSION: Patients with Meniere's disease could have a saccular dysfunction (54% in this series). This saccular impairment correlated with low frequency hearing loss but not with canal paresis. Patients without VEMPs had poorer postural performances in condition 5 than those with normal VEMPs. Therefore, VEMP testing is useful for detecting patients at risk: in patients with saccular lesion, the dynamic postural performances should be assessed on a movable platform to detect visually dependent patients and to orient vestibular rehabilitation.     

Modulation of GABA receptor subunits in rat facial motoneurons after axotomy

Facial nerve axotomy is a good model for studying neuronal plasticity and regeneration in the peripheral nervous system. In the present study, we investigated the effect of axotomy on the different subunits of GABA(A) and GABA(B) receptors of facial motoneurons. The facial nerve trunk was unilaterally sectioned and operated rats were sacrificed at 1, 3, 8, 30, and 60 days later. mRNAs coding for alpha1, beta2, and gamma2 of GABA(A) receptors and for GABA(1B) and GABA(B2) receptors were down-regulated by axotomy. This decrease began as soon as 1 or 3 days after axotomy, and the minimum was 8 days post-lesion; the mRNA levels remained lower than normal at day post-lesion 60. The abundance of mRNAs coding for the three other alpha2, beta1, and beta3 facial subunits of GABA(A) receptors and for the pre-synaptic GABA(B1A) subunit remained unchanged during the period 1-8 days post-lesion. Immunohistochemistry using specific antibodies against alpha1, gamma2 subunits of GABA(A) and against GABA(B2) subunits confirmed this down-regulation. Colchicine treatment and blockade of action potential by tetrodotoxin significantly decreased GABA(A)alpha1 immunoreactivity in the axotomized facial nucleus after 7 days. Finally, muscle destruction by cardiotoxin or facial palsy induced by botulinum toxin failed to change GABA(A)alpha1 subunit expression. Our data demonstrate that axotomy strongly reduced the amounts of alpha1, beta2, and gamma2 subunits of GABA(A) receptors and B(1B) and B(2) subunits of GABA(B) receptors in the axotomized facial motoneurons. The loss of GABA(A)alpha1 subunit was most probably induced by both the loss of trophic factors transported from the periphery and a positive injury signal. It also seems to be dependent on activity disruption.     

The use of the activated clotting time for monitoring heparin therapy in critically ill patients

OBJECTIVE: To determine the correlation between activated clotting time (ACT) and activated partial thromboplastin time (aPTT) in patients receiving intravenous unfractionated heparin therapy, and the accuracy of the ACT in predicting the level of anticoagulation. DESIGN: Paired aPTT and ACT measurements were obtained from a convenience sample of critically ill patients requiring intravenous unfractionated heparin. The aPTT was determined in the hospital laboratory and ACT measurements were performed with a portable device. SETTING: The intensive care unit of Ghent University Hospital, a tertiary care facility with 54 beds. PATIENTS AND PARTICIPANTS: Twenty-eight patients were studied prospectively; a total of 105 paired samples were obtained. The indication for heparin therapy was cerebral ischemia in 8, various cardiac conditions in 10, pulmonary embolism in 3, continuous hemofiltration in 3, and peripheral arterial thrombosis in 4. RESULTS: There was a significant correlation between aPTT and ACT. Analysis of variance showed a significant difference in ACT between different levels of anticoagulation, aPTT shorter than 60 s (group 1), aPTT 60-90 s (group 2), and aPTT longer than 90 s (group 3): 142+/-16.7 s in group 1 vs. 155+/-29.6 and 192+/-39.1 in groups 2 and 3. CONCLUSIONS: The correlation between the aPTT and the ACT in this ICU setting is poor; ACT cannot differentiate between low and therapeutic levels of anticoagulation. The use of the ACT for monitoring low to moderate doses of heparin in ICU patients cannot be recommended.     

Monitoring nasal allergic inflammation by measuring the concentration of eosinophil cationic protein and eosinophils in nasal secretions

Quantitative measurement of the eosinophil cationic protein (ECP) concentration and the percentage of eosinophils in nasal secretions has greatly improved our understanding of the inflammatory process after natural allergen exposure. ECP and eosinophils were measured in the nasal secretions of 40 symptomatic patients with seasonal allergic rhinitis during the pollen season. Results showed a significant relationship between a high concentration of ECP (median: 410 ng/g, range: 6–2380 ng/g) and a high percentage of eosinophils (median: 13.5%, range: 1–85%). This quantitative study again demonstrated that infiltration by eosinophils and release of ECP play a key role in allergic rhinitis. It also suggests that the combined measurement of the percentage of eosinophils together with the ECP concentration in nasal secretions seems to be a very useful model in monitoring and assessing the condition of chronic nasal inflammation in patients with allergic rhinitis.     

Hematologic values and lymphocyte subsets in fetal blood

Hematologic values and lymphocyte subpopulations were determined in normal fetal blood during the second trimester of gestation. In these samples the platelet, erythrocyte, and leukocyte counts were significantly lower than in adults. Large red blood cells with a high hemoglobin content were present. Before the twentieth week of gestation, erythroblasts made up about half of the nucleated elements. Lymphocytes formed most of the leukocytes, and their absolute numbers were comparable to those in adults. Most of the fetal blood lymphocytes expressed T- or B-cell surface differentiation antigens. The percentage of T-cells was lower and that of B-cells was higher than in the adult. A high OKT4/OKT8 ratio was present. It was due to a low percentage of OKT8-positive cells. Lymphocytes with a natural killer cell phenotype were rare. Most lymphocytes were OKT10 positive, but almost none reacted with the antithymocyte antibody OKT6. These results give additional information about the development of blood cells in early human life. They can be used as reference values for the prenatal diagnosis of hereditary or acquired anomalies of the hematologic and immunologic systems.     

Southern blot analysis in a case of Richter's syndrome. Evidence for a postrearrangement heavy chain gene deletion associated with the altered phenotype.

Richter's syndrome (RS) can be defined as the emergence of an aggressive lymphoma in patients suffering from chronic lymphocytic leukemia (CLL). The authors performed immunophenotypic and Southern blot analysis of the peripheral blood and tissue specimen of a patient with RS. Using immunoperoxidase and immunogold-silver staining techniques and a panel of monoclonal antibodies, the authors found that the large cells characteristic of RS showed an altered immunophenotype as compared with the CLL cells and did not express mu heavy chain. Southern blot analysis revealed identical kappa light chain rearrangements in both tumoral cell populations consistent with a common clonal origin. Using the JH probe and several restriction enzymes, the authors also found evidence for a postrearrangement deletion of the heavy chain mu gene. These findings suggest that in this case of RS, a deletion of the heavy chain mu gene resulted in loss of mu expression by the larger cells that were characteristic of RS and was associated with their altered phenotype.