Levetiracetam as first-line monotherapy for Idiopathic Generalized Epilepsy in women.

BACKGROUND: Levetiracetam (LEV) is effective in Idiopathic Generalized Epilepsy (IGE) and seems to be a good alternative to valproic acid in women of childbearing age. However, there is lack of approval for this indication as monotherapy. The aim of this study is to assess the efficacy of LEV as a first-line therapy in this population. METHODS: The study is a descriptive analysis of women aged between 16 and 45 years old diagnosed with IGE and treated with LEV as first-line monotherapy. Minimum follow-up was 24 months. RESULTS: 26 women. Mean age: 25.4 years (17-43). 14 Juvenile Myoclonic Epilepsy; 8 Tonic-Clonic Seizures Alone; 4 Juvenile Absence. Mean follow-up: 68.3 months (24-120). 11 patients (40.7%) continued to take LEV as monotherapy, of which 10 were seizure-free, and three (11.5%) continue to be seizure-free after withdrawing LEV. 12 patients (46.2%) required a change of treatment: 25% (3/12) due to lack of efficacy, 42% (5/12) due to adverse effects and 33% (4/12) due to both. Irritability was the most frequent adverse effect. At the last assessment, three patients (11.5%) continued to have seizures despite polytherapy. Estimated retention rates were 78.1% at one year (SE 7.3%) and 51% at 5 years (SE 9.8%). Estimated median retention time is 72 months (CI 95%: 50.9-93.1). CONCLUSION: LEV could be an effective drug as first-line treatment for IGE in women of childbearing potential. The adverse effects are its main limitation. Comparative studies are needed in order to establish it for this indication.

Low penetrance, broad resistance, and favorable outcome of interleukin 12 receptor beta1 deficiency: medical and immunological implications.

The clinical phenotype of interleukin 12 receptor beta1 chain (IL-12Rbeta1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rbeta1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guérin -BCG- and environmental Mycobacteria). Three patients had clinical tuberculosis, one of whom also had salmonellosis. Unlike salmonellosis, mycobacterial infections did not recur. BCG inoculation and BCG disease were both effective against subsequent environmental mycobacteriosis, but not against salmonellosis. Excluding the probands, seven of the 12 affected siblings have remained free of case-definition opportunistic infection. Finally, only five deaths occurred in childhood, and the remaining 36 patients are alive and well. Thus, a diagnosis of IL-12Rbeta1 deficiency should be considered in children with opportunistic mycobacteriosis or salmonellosis; healthy siblings of probands and selected cases of tuberculosis should also be investigated. The overall prognosis is good due to broad resistance to infection and the low penetrance and favorable outcome of infections. Unexpectedly, human IL-12 is redundant in protective immunity against most microorganisms other than Mycobacteria and Salmonella. Moreover, IL-12 is redundant for primary immunity to Mycobacteria and Salmonella in many individuals and for secondary immunity to Mycobacteria but not to Salmonella in most.

Neonatal rigid-akinetic syndrome and dentato-olivary dysplasia.

This report describes a male infant who presented since birth with rigidity and hypokinesia. Severe developmental delay, episodic central hypoventilation, and drug-resistant epilepsy progressively added to the extrapyramidal signs in the following months and led to the patient's death at 10 months of age. Neuroradiologic and neurometabolic evaluations were negative. Normal cerebrospinal metabolites excluded a defect in dopamine metabolism, and treatment with levodopa failed to improve his motor symptoms. Neuropathologic findings demonstrated dentato-olivary dysplasia. While isolated dentato-olivary dysplasia has been described in a few cases of Ohtahara syndrome, to our knowledge, the association with infantile parkinsonism has not been previously reported.

Clinical tuberculosis in 2 of 3 siblings with interleukin-12 receptor beta1 deficiency.

We describe 3 siblings with interleukin-12 receptor beta1 (IL-12Rbeta1) deficiency, a known genetic etiology of clinical disease caused by infection with poorly virulent mycobacteria, such as mycobacteria found in bacille Calmette-Guérin (BCG) vaccines and environmental nontuberculous mycobacteria (NTM). One child had disseminated tuberculosis, the second had extraintestinal salmonellosis and pulmonary tuberculosis, and the third remained asymptomatic. IL-12Rbeta1 deficiency should be considered as a diagnosis in patients with severe salmonellosis or tuberculosis, even if they do not have disease due to BCG or NTM.

Usefulness of intravenous lacosamide in status epilepticus.

Lacosamide (LCM) is a treatment option for status epilepticus (SE) described in several series. We therefore proposed to describe its use in status epilepticus patients in our hospital. All patients admitted to our hospital for SE from September 2010 to April 2012 were evaluated. We collected related variables including the type of SE, etiology, antiepileptic drugs (AEDs) used, loading dose of AEDs, cessation of SE after AEDs, ICU admission and mortality. In those patients receiving LCM, we reviewed the infusion rate and time to response. We compared patients receiving LCM with patients in whom it was not used. This was a retrospective and uncontrolled study. A total of 92 patients were included; 67.7 % of SE patients who received LCM responded to treatment. The vast majority of the patients presented non-convulsive and motor focal SE. When we selected patients to receive four or more AEDs, the LCM efficacy was 55.6 %, a very similar result compared to when it was not used. Subsequently, we analyzed the sample regarding the AED administered as the second or third line of treatment, and the responder rate was significantly higher when LCM was used (84.6 vs. 47.8 %, p 0.041). After an adjusted regression analysis, the use of LCM was independently associated with cessation of SE. The total percentage of undesirable effects was very low (12 %), and they were all mild. No relationship was found between a specific etiology and better response. LCM is a useful drug that represents an alternative in the treatment of non-convulsive or focal motor SE. Its efficacy might be more important when it is administered as a second or third option after benzodiazepines. A randomized trial is required to confirm these results.

Progressive vacuolating glycine leukoencephalopathy with pulmonary hypertension.

To report two unrelated patients with a new phenotype of nonketotic hyperglycinemia associated with idiopathic pulmonary hypertension. Clinical findings included rapidly progressive neurological deterioration with onset in the first year of life characterized by developmental regression without seizures or electroencephalogram abnormalities during follow-up. Both patients died before the age of 18 months. Glycine cleavage system deficiency was confirmed by enzymatic studies in frozen liver. Molecular analysis in the related genes showed no pathogenic mutation. Radiological and pathological findings were consistent with progressive vacuolating encephalopathy. Our patients with biochemical and enzymatic parameters consistent with atypical nonketotic hyperglycinemia. The clinical and radiological evolution, as progressive vacuolating leukoencephalopathy and the association with pulmonary hypertension constitute a previously unrecognized variant.