Etiological assessment of status epilepticus.

Status epilepticus (SE) is a potentially serious condition that can affect vital and functional prognosis and requires urgent treatment. Etiology is a determining factor in the patient's functional outcome and in almost half of all cases justifies specific treatment to stop progression. Therefore, identifying and addressing the cause of SE is a key priority in SE management. However, the etiology can be difficult to identify among acute and remote causes, which can also be multiple and interrelated. The most common etiologies are the discontinuation of antiepileptic medication in patients with a prior history of epilepsy, and acute brain aggression in cases of new onset SE (cerebrovascular pathologies are the most common). The list of remaining possible etiologies includes heterogeneous pathological contexts. Refractory SE and especially New-Onset Refractory Status Epilepticus (NORSE) lead to an extension of the etiological assessment in the search for encephalitis of autoimmune or infectious origin in adults and in children, as well as a genetic pathology in children in particular. This is an overview of current knowledge of SE etiologies and a pragmatic approach for carrying out an etiological assessment based on the following steps: - Which etiological orientation is identified according to the field and clinical presentation?; - Which etiologies to look for in an inaugural SE?; - Which first-line assessment should be carried out? The place of the biological, EEG and imaging assessment is discussed; - Which etiologies to look for in case of refractory SE?

Variability of sweat chloride concentration in subjects with cystic fibrosis and G551D mutations.

INTRODUCTION: Sweat chloride concentration, a biomarker of CFTR function, is an appropriate outcome parameter in clinical trials aimed at correcting the basic CF defect. Although there is consensus on a cut-off value to diagnose CF, we have only limited information on the within subject variability of sweat chloride over time. Such information would be useful for sample size calculations in clinical trials. Therefore, we retrospectively analyzed repeated sweat chloride values obtained in patients with G551D mutation(s) assigned to placebo in an ivacaftor interventional trial. METHODS: In subjects with G551D at least 12years of age, a pilocarpine sweat test using Macroduct collector was taken on both arms at 8 time points over 48weeks. We explored 1062 pilocarpine sweat test values obtained in 78 placebo patients of the VX08-770-102 trial. RESULTS: Mean overall sweat chloride value (all patients, all tests, n=1062) was 100.8mmol/L (SD 12.7mmol/L). Using a multilevel mixed model, the between-subject standard deviation (SD) for sweat chloride was 8.9mmol/L (95% CI 7.4-10.6) and within-subject SD was 8.1mmol/L (95% CI 7.5-8.7). Limits of repeatability for repeat measurements were -19.7 to +21.6mmol/L using values from one arm, and -13.3 to 11.8mmol/L using mean of values obtained at 4 test occasions. Sample size calculations showed that the minimal treatment effect on sweat chloride concentration that can be demonstrated for a group of 5 patients is around 15mmol/L, using a cross-over design and combinations of 4 tests for each phase of the trial. CONCLUSION: Although the sweat test is considered a robust measure, sweat chloride measurements in patients with CF and a G551D mutation had an inherent biological variability that is higher than commonly considered. Further analyses of placebo group data are crucial to learn more about the natural variability of this outcome parameter.

[Value of lumbar puncture after a first febrile seizure in children aged less than 18 months. A retrospective study of 157 cases]. / Utilité de la ponction lombaire lors de la première convulsion fébrile chez l'enfant de moins de 18 mois. Étude rétrospective de 157 cas.

AIM: Because meningitis symptoms are not very specific under the age of 18 months, lumbar puncture (LP) was widely recommended in children presenting a febrile seizure (FS). Recent retrospective studies have challenged this age criterion. In 2011, the American Academy of Pediatrics updated its guidelines for the first episode of simple FS: LP is indicated if signs suggestive of meningitis are present and remains "an option" in case of prior antibiotic treatment or between the age of 6 and 12 months if the child is not properly vaccinated against Haemophilus and Streptococcus pneumoniae. Because the meningitis epidemiology and the vaccination coverage are different, the objective of this study was to evaluate whether these new guidelines were applicable in France. PATIENTS AND METHODS: Between 2009 and 2010, we conducted a retrospective single-center study including 157 children aged less than 18 months admitted to the pediatric emergency department (Children's Hospital, Toulouse, France) for their first febrile seizure. The data collected were: type of seizure, knowledge of prior antibiotic treatment, neurological status, signs of central nervous system infection, and biological results (LP, blood cultures). RESULTS: Lumbar puncture was performed in 40% of cases (n=63). The diagnosis of meningitis/encephalitis was selected in eight cases: three cases of viral meningitis, three bacterial meningitis (Streptococcus pneumoniae), and two non-herpetic viral encephalitis. The incidence of bacterial meningitis in our study was 1.9%. The risk of serious infection, bacterial meningitis or encephalitis, was increased when there was a complex FS (14% versus 0% with a simple FS, P=0.06). The presence of other suggestive clinical symptoms was strongly associated with a risk of bacterial meningitis/encephalitis (36% in case of clinical orientation versus 0% in the absence of such signs, P<0.001). DISCUSSION: All severe clinical presentations were associated with complex FS (prolonged, focal, and/or repeated seizures) and the presence of other suggestive clinical signs (impaired consciousness lasting longer than 1h after the seizure, septic aspect, behavior disorders, hypotonia, bulging fontanel, neck stiffness, petechial purpura). The risk of bacterial meningitis or encephalitis associated with a simple FS and followed by a strictly normal clinical examination is extremely low. CONCLUSION: After a simple febrile seizure without any other suggestive signs of meningitis, systematic lumbar puncture is not necessary even in children younger than 18 months. LP remains absolutely indicated if clinical symptoms concentrate on central nervous system infection and should be discussed in case of complex seizures, prior antibiotic treatment, or incomplete vaccination.

[Respiratory syncytial virus brainstem encephalitis in a 7-year-old boy]. / Rhombencéphalite liée au virus respiratoire syncytial chez un garçon de 7 ans.

The literature reports that neurological complications of childhood respiratory diseases due to respiratory syncytial virus (RSV) fluctuate between 1 and 40% of cases. They mostly involve central apnea - often the first symptom of infection - anoxia, and ischemic brain damage due to severe sudden weakness in infants, and seizures and consciousness disorders more or less associated with focalized neurological deficiency proving an encephalitis lesion. We report the case of brainstem encephalitis in a 7-year-old boy with RSV A nasopharyngitis, with meningitis, positive polymerase chain reaction in cerebrospinal fluid and magnetic resonance imaging (MRI) abnormalities, which was explained by viral replication encephalitis. Based on a literature review, we discuss the main aspects of epidemiology and physiopathology of the main neurological complication of RSV. Most of them have not been fully investigated and only a few articles report encephalitis. As far as central apnea is concerned, an animal experimental hypothesis surprisingly suggests a peripheral mechanism.

[The outcome of children presenting with a prenatally diagnosed arachnoid cyst]. / Devenir des enfants présentant un kyste arachnoïdien de diagnostic anténatal.

AIM: Evaluate the outcome of children with prenatally diagnosed arachnoid cysts. MATERIAL AND METHODS: Retrospective study of seventeen cases of children who were diagnosed with an arachnoid cyst during prenatal MRI between July 1994 and January 2007 and followed up for a mean 6 years and 6 months. Follow-up was based on evaluation of clinical files and contacts with the physicians who were following the children. The children were divided into three groups: group 1 normal development, group 2: minor clinical signs, normal schooling, group 3: major clinical symptoms, schooling disturbed. RESULTS: Eight of the 17 patients included in this study underwent derivation surgery for the cyst. Eight of the 17 children were in group 1, and 3 in group 2. Four of the 6 children in group 3 had associated symptoms. Two of the children in group 3 present with a supratentorial cyst, and 4 with a cyst of the posterior fossa. CONCLUSION: The prenatal diagnosis of a arachnoid cyst should be accompanied by a search for associated lesions. The risk of hydroencephalitis should be explained to the parents.

Metabolic disorders and chronic viral disease: the case of HIV and HCV.

The importance of metabolic disorders in the pathophysiology of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections is becoming increasingly apparent. Metabolic anomalies, with their potential for multiple-organ involvement, are to be expected, given the chronic nature of these diseases, and the intracellular dysregulation associated with them. Not only have the endocrine and cytokine metabolic anomalies seen in HIV and HCV infections been linked with the metabolic syndrome, but they also appear to have some pathways in common. Studying the differences and similarities between these metabolic anomalies may add to our understanding of HIV and HCV infection, and provide guidance on how to treat these chronic diseases. This review highlights the principal underlying factors for metabolic disorders in these chronic viral diseases-namely insulin resistance and liver damage. Both the chronic viral state itself and the host immune response give rise to glucose and lipid metabolic disorders that, in turn, are risk factors for hepatic damage. The various interactions between HIV and/or HCV with insulin resistance, type 2 diabetes, steatosis and fibrogenesis should be considered when determining the treatment and long-term follow-up of patients. Recent data indicate that HCV clearance improves insulin resistance and hepatic function in HCV-infected patients treated with interferon with or without ribavirin.

[Adherence to antiretroviral therapy during HIV infection, a multidisciplinary approach]. / "L'observance thérapeutique au cours de l'infection VIH, une approche multidisciplinaire".

Since HIV infection has become a chronic disease, antiretroviral therapy is now used on a long-term basis. Response to treatment is conditioned by numerous inter-dependent factors, including non-compliance, which can result in failure of the therapeutic regimen. Although compliance is crucial for long-term efficacy of the treatment, it is a dynamic factor, and therefore difficult to evaluate. This literature review proposes a multidisciplinary approach to treatment adherence during HIV infection, and deals with the following questions: how should adherence and non-adherence be defined? How are they correlated to the treatment response? How is adherence measured in trials and cohorts, as well as in clinical practice? By what factors is it influenced? What tools can be implemented to improve adherence? The interaction between adherence and response to antiretroviral therapy requires communication between clinicians, healthcare providers, patients, virologists, pharmacologists, and the companies responsible for developing drugs. The pharmaceutical industry must sustain its efforts to ensure a balance between demands for efficacy and adherence when developing new drugs. And the methods implemented by numerous healthcare teams plead in favour of a dynamic approach to adherence, with the active participation of all.