Clinical and neuroimaging characteristics of 14 patients with prionopathy: a descriptive study.

INTRODUCTION: Prionopathy is the cause of 62% of the rapidly progressive dementias (RPD) in which a definitive diagnosis is reached. The variability of symptoms and signs exhibited by the patients, as well as its different presentation, sometimes makes an early diagnosis difficult. METHODS: Patients withdiagnosis of definite or probable prionopathy during the period 1999-2012 at our hospital were retrospectively reviewed.The clinical features and the results of the complementary tests (14-3-3 protein, EEG, MRI, FDG-PET, and genetic analysis) were evaluated in order to identify some factors that may enable an earlier diagnosis to be made. RESULTS: A total of 14 patients are described: 6 with definite sporadic Creutzfeldt-Jakob (sCJD) disease, 3 with probable sCJD, 4 with fatal familial insomnia, and 1 with the new variant. The median age at diagnosis was 54 years old. The mean survival was 9.5 months. Mood disorder was the most common feature, followed by instability and cognitive impairment. 14-3-3 protein content in the cerebrospinal fluid was positive in 7 of 11 patients, and the EEG showed typical signs in 2 of 12 patients. Neuroimaging (FDG-PET, MRI) studies suggested the diagnosis in 13 of the 14 patients included. CONCLUSIONS: Most patients presenting with RPD suffer from a prion disease. In our series the most useful complementary tests were MRI and FDG-PET, being positive in 13 of the 14 patients studied.

Identifying single molecular ions by resolved sideband measurements.

The masses of single molecular ions are nondestructively measured by cotrapping the ion of interest with a laser-cooled atomic ion, (40)Ca(+). Measurement of the resolved sidebands of a dipole forbidden transition on the atomic ion reveals the normal-mode frequencies of the two ion system. The mass of two molecular ions, (40)CaH(+) and (40)Ca(16)O(+), are then determined from the normal-mode frequencies. Isotopes of Ca(+) are used to determine the effects of stray electric fields on the normal mode measurement. The future use of resolved sideband experiments for molecular spectroscopy is also discussed.

The np Rydberg series of boron monohydride: l-uncoupling and its evolution for intermediate principal quantum numbers n = 4 to n = 11.

Using optical-optical-optical triple-resonance spectroscopy, we assign rotational levels with N = 0-5 in the vibrationless, lower-n, p Rydberg states of (11)BH. We apply the Hill and Van Vleck formulation for energy levels with l = 1 in a Hund's case intermediate between (b) and (d) to gauge the energy separating (1)Π and (1)Σ(+) states with zero rotation for n = 4-11. This energy difference, A(l, ξ), represents the strength of the coupling, ξ, between the electron orbital angular momentum, l, and the internuclear axis, which determines the Λ-splitting constant, q(0). The np series exhibits a large q(0) that increases monotonically with n to reach a magnitude similar to the rotational constant, B(0), by n = 9. For higher principal quantum numbers, Λ ceases to be a good quantum number, and l-uncoupling becomes virtually complete for n > 10.

The np Rydberg series of boron monohydride: l-uncoupling and Rydberg electron interactions with the rovibrational motion of the ion core.

A simple two-channel quantum defect theory approach accounts for resonance positions in the np Rydberg series of (11)BH. The transition from Hund's case (b) to (d) in the interacting levels of this np series represents a fundamental example of electron orbital ⇔ cation core rotational coupling, and frame transformation theory offers a means to connect close-coupled electronically excited-state potentials and l-uncoupled Rydberg positions. This evolving interaction of the np Rydberg electron with the rotational and the vibrational motion of the (11)BH(+) core is formulated in terms of quantum defects, µ(λ)(v(+)).

Infrared spectra of C2H6, C2H4, C2H2, and CO2 aerosols potentially formed in Titan's atmosphere.

Pure and mixed aerosols of ethane, ethylene, acetylene and carbon dioxide were generated in a collisional cooling cell and characterized by Fourier transform infrared spectroscopy between 600 and 4000 cm(-1). Pure ethane, pure ethylene, and mixed ethane/ethylene initially form supercooled liquid droplets, which over time crystallize to their stable solid phases. These droplets are found to be long-lived (up to hours) for pure ethane and mixed ethane/ethylene, but short-lived (up to seconds) for pure ethylene. Acetylene and carbon dioxide form solid aerosol particles. Acetylene particles have a partially amorphous structure, while carbon dioxide particles are crystalline. The structure of the infrared bands of carbon dioxide is strongly determined by the particles' shape due to exciton coupling. The comparison of various mixed systems reveals that acetylene very efficiently induces heterogeneous crystallization. As reported earlier, the co-condensation of acetylene and carbon dioxide can lead to the formation of a metastable mixed crystalline phase. Our preliminary calculations show that this mixed phase has a monoclinic rather than the cubic structure proposed previously.

LC method for the therapeutic drug monitoring of lamotrigine: evaluation of the assay performance and validation of its application in the routine area.

An accurate and precise high-performance liquid chromatographic method using diode array detection for the determination of lamotrigine in human plasma has been developed and validated for use in pharmacokinetic studies. A validation strategy based on the accuracy profiles was used to select the most appropriate regression model and to determine the limits of quantitation as well as the concentration range. On the other hand, the present paper also shows this validation approach as a suitable tool to guaranty the quality of the results obtained by the use of the analytical validated methodology for plasma lamotrigine determination in a routine setting and to ensure the risk of obtaining the future measurements outside the previously fixed acceptance limits.

[Management of first epileptic seizure and status epilepticus in the emergency department]. / Manejo de la primera crisis epiléptica y del status en urgencias.

First epileptic seizure is a common reason for attending the emergency department. Its management is focused on diagnosis of the episode and on identification and treatment of the underlying cause. Occasionally, anti-epileptic treatment will be required. However, when the seizure is prolonged - a condition known as status epilepticus - it becomes a life-threatening process and requires immediate treatment. In this article, general advice and guidelines for the management of seizures and of status epilepticus in emergency departments is reviewed.

Occurrence of chlorinated volatile organic compounds (VOCs) in a sanitary sewer system: Implications for assessing vapor intrusion alternative pathways.

Sewer systems have been recently recognized as potentially important exposure pathways to consider during vapor intrusion assessments; however, this pathway has not been well-characterized and there is need for additional information about the occurrence of volatile organic compounds (VOCs) in sewer systems. This paper reports the results of sewer gas sampling conducted in a sanitary sewer over the years of 2014-2017. Sewer gas samples were collected and analyzed using several different techniques, including TO-15 (grab), TO-17 (passive), Radiello® (passive) and a novel continuous monitoring technique, the Autonomous Rugged Optical Multigas Analyzer (AROMA). The applicability of each of the different approaches used in this study is discussed in the context of investigating sanitary sewers as a vapor intrusion alternative pathway. The data confirmed that trichloroethylene (TCE) concentrations in sewer gas were detected adjacent to and extending hundreds of feet away from a previously defined vapor intrusion area, where TCE was a primary contaminant. TCE concentrations detected in sewer gas ranged from non-detect to 1600µg/m3. Temporal variability was observed in TCE concentrations over timescales that ranged from minutes to months to years at discrete sampling locations. Spatial variability in sewer gas concentrations was also observed throughout the study area. Temporal and spatial variability may be caused by groundwater contamination sources in the study area, as well as sewer gas transport mechanisms.

EPICON consensus: recommendations for proper management of switching to eslicarbazepine acetate in epilepsy. / Consenso Delphi EPICON: recomendaciones sobre el manejo adecuado del cambio a acetato de eslicarbazepina en epilepsia.

INTRODUCTION: The objective of the EPICON Project is to develop a set of recommendations on how to adequately switch from carbamazepine (CBZ) and oxcarbazepine (OXC) to eslicarbazepine acetate (ESL) in some patients with epilepsy. METHODS: A steering committee drafted a questionnaire of 56 questions regarding the transition from CBZ or OXC to ESL in clinical practice (methodology and change situation). The questionnaire was then distributed to 54 epilepsy experts in 2 rounds using the Delphi method. An agreement/disagreement consensus was defined when a median ≥ 7 points or ≤ 3 was achieved, respectively, and a relative interquartile range ≤ 0.40. We analysed the results obtained to reach our conclusions. RESULTS: Our main recommendations were the following: switching from CBZ to ESL must be carried out over a period of 1 to 3 weeks with a CBZ:ESL dose ratio of 1:1.3 and is recommended for patients who frequently forget to take their medication, those who work rotating shifts, polymedicated patients, subjects with cognitive problems, severe osteoporosis-osteopaenia, dyslipidaemia, or liver disease other than acute liver failure, as well as for men with erectile dysfunction caused by CBZ. The transition from OXC to ESL can take place overnight with an OXC:ESL dose ratio of 1:1 and it is recommended for patients who frequently forget to take their medication, those who work rotating shifts, polymedicated patients, or those with cognitive problems. The transition was not recommended for patients with prior rash due to CBZ or OXC use. CONCLUSION: The EPICON Project offers a set of recommendations about the clinical management of switching from CBZ or OXC to ESL, using the Delphi method.

[Epilepsy and sleep]. / Epilepsia y sueño.

The relationship between sleep and epilepsy is known from more than a century ago. At the end of the XIXth century a temporal relationship between the onset of epileptic seizures and the wake-sleep cycle was observed. The introduction of the electroencephalogram allowed establishing the effect of sleep and sleeping deprivation on epileptiform interictal discharges and on epileptic seizures. The recognition of the variety of generalized and partial epileptic syndromes associated to sleep is important to make a correct differential diagnosis of patients presenting with motor and behavioural disturbances of sleep. This article reviews the different aspects of the relationship between epilepsy and sleep.

A study of thin film solid phase microextraction methods for analysis of fluorinated benzoic acids in seawater.

Fluorinated benzoic acids (FBAs) are frequently used as tracers by the oil industry to characterize petroleum reservoirs. The demand for fast, reliable, robust, and sensitive approaches to separate and quantify FBAs in produced water, both in laboratory and field conditions, has not been yet fully satisfied. In this study, for the first time, thin film solid phase microextraction (TF-SPME) is proposed as a versatile sample preparation tool for the determination of FBAs in produced water by pursing two different approaches. First, an automated high throughput TF-SPME method using solvent desorption for fast and simultaneous preparation of multiple samples prior to liquid chromatographic separation and high resolution mass spectrometric detection (LC-MS) of FBAs was demonstrated for routine laboratory analysis. This method was optimized in terms of extraction phase chemistry, sample pH and ionic strength, extraction/desorption times using two representative FBAs (4-FBA and 2,3,4,5-tetra FBA). It incorporates a relatively simple sample pretreatment involving pH adjustment prior to the TF-SPME, and obtained limits of quantification (LOQ) are at the 1.0ngmL(-1) level. Second, the applicability of TF-SPME for fast mass spectrometric (MS) determination of FBAs with omission of derivatization and gas chromatographic (GC) separation was proven. This second method consists of manual extractions of analytes from seawater samples with a thermally stable TF-SPME membrane and direct thermal desorption of the extracted FBAs to a MS via a thermal desorption unit (TDU). It was demonstrated that the TF-SPME extracts and thermally releases analytes quantitatively and with good reproducibility. This approach opens up the possibility for on-site measurements with portable analyzers.

Double-blind, placebo-controlled study of topiramate in patients with refractory partial epilepsy.

The efficacy and safety of topiramate 400 mg/day as adjunctive therapy to traditional antieleptic drugs for partial onset seizures with or without secondary generalization were assessed in a double-blind, parallel-group, placebo-controlled trial. Forty-seven patients with at least one seizure per week during an 8 week baseline were randomly assigned to topiramate (N = 23) or placebo (N = 24) double-blind treatment for a 3 week titration and an 8 week stabilization period. Median percent reduction from baseline in monthly seizure frequency during the double-blind phase was not significantly greater in the topiramate group than in the placebo group (41% vs. 1%; P = 0.065). Nevertheless, other efficacy variables evidenced statistically significant differences in favor of topiramate: a greater number of treatment responders (> or = 50% reduction in seizures; 35% vs. 8%; P = 0.033); better investigator (P = 0.002) and patient (P = 0.021) global assessments; and greater reductions in secondarily generalized seizures compared to placebo (P = 0.002). The most commonly reported topiramate treatment-emergent adverse events were somnolence, fatigue, abnormal vision, weight decrease, and anxiety. Most adverse events were mild or moderate in severity. Among 7 withdrawals due to limiting adverse events, 6 were CNS-related (in 5 topiramate-treated patients). Results of this trial strongly suggest that topiramate 400 mg/day is effective and well tolerated in the treatment of refractory partial epilepsy.

Toxic myoclonus.

Several toxins produce encephalopathies in which myoclonus can be a prominent feature. These include intoxications with bismuth, methyl bromide, cooking oil containing anilines, and tetraethyl lead. The clinical features in many cases resemble the action myoclonus syndrome of posthypoxic encephalopathy.

[Safety and tolerability of gabapentin]. / Seguridad y tolerabilidad de la gabapentina.

OBJECTIVE: To review the information available regarding the safety and tolerability of gabapentin (GBP) in the treatment of epilepsy. PATIENTS AND METHODS: We reviewed the reports in the literature on the safety, adverse effects and tolerance of GBP as treatment, used as monotherapy or associated with other drugs, in epilepsies in patients of all age groups, including children, adults and the elderly. RESULTS: All published studies confirm that GBP is a well tolerated drug when used for monotherapy or associated with other antiepileptic drugs. The commonest adverse effects seen were somnolence, fainting, ataxia, nystagmus, tremor and headache. However, their incidence was low and intensity mild. There was no clear relationship between the dose given and appearance of side effects, except for fainting and somnolence. CONCLUSIONS: GBP is a drug which is free of unwanted side effects. Its safety and tolerability profile is excellent for treatment of simple and complex partial crises, with or without generalization in epileptic patients of all ages.

[How often and what type of control tests should be done during long- term anti-epileptic treatment?]. / Con qué frecuencia y qué tipo de controles deben realizarse durante el tratamiento antiepiléptico crónico?

During long-term epileptic treatment, it is essential to monitor the efficacy of the drugs used. Any adverse effects of this treatment must be detected early or preferably avoided. However, the type of control and the frequency with which this should be carried out are controversial. All anti-epileptic drugs are potentially liable to provoke adverse reactions of different types and degrees. Determinations of the blood-levels of anti-epileptic drugs are useful to attain optimus drug levels, and to identify any relationship there might be between these drugs and possible adverse effects. However, this usefulness varies, depending on the particular anti-epileptic drug concerned. Therefore measurement as a routine is not justified, but should be undertaken to obtain the answer to specific questions. Laboratory analysis of blood to determine liver function, blood cell counts, coagulation, etc. is necessary in some cases. This may imply problems of interpretation and of cost. Is most cases it is of little help in the early detection or prevention of the most serious adverse reactions, which cause the greatest mortality. Therefore although such measures are necessary, attention should be paid to clinical methods for the early detection of symptoms and signs which may indicate the presence of adverse effects. Similarly, EEG should not be done as a routine for the assessment of the effect of treatment, but should be used when indicated for the follow-up of specific epileptic syndromes. An EEG may be useful for prognosis before suspending long-term epileptic treatment.

[Overall treatment of vascular epilepsy]. / Tratamiento global de la epilepsia vascular.

Cerebrovascular disease has different acute, ischemic and hemorrhagic presentations and may be associated with epileptic crises during the acute phase, or a later epileptic syndrome may develop. Status epilepticus is an infrequent complication which may appear at any time during the course of the illness, sometimes as the first and only sign of epilepsy. The risk of acute crises or of an epileptic syndrome varies depending on the nature of the vascular accident: its occurrence is more likely in hemorrhagic lesions and in those involving the cerebral cortex. The acute crises may be treated with benzodiazepines or with fast acting antiepileptic drugs; parenteral administration may sometimes be necessary. The need for prolonged prophylactic antiepileptic treatment is still under discussion, since there is no evidence that this prevents later development of an epileptic syndrome. The management of status epilepticus is the same whatever the etiology, although one has to take account of the risk of side-effects related to the age and general health of the patient. When deciding on treatment for vascular epilepsy consideration should be given not only to which drugs are to be used, but also their pharmacokinetic characteristics and interactions with any treatment required by the patient for coexisting conditions such as arterial hypertension, heart failure, anticoagulation, diabetes, etc.

[Prolonged monitoring with video-EEG. Clinical applications]. / Monitorización prolongada de vídeo-EEG. Aplicaciones clínicas.

INTRODUCTION: The differential diagnosis of paroxysmal events include a large number of entities. A careful diagnosis is needed because of the specific treatment that most of them require. If a mistake is done in the diagnosis, the consequences in the treatment may be relevant, not only because the maintenance of the episodes but because the secondary effects of the wrong medications. The video-EEG monitoring is key when the diagnosis of epileptic seizures is suspected. However, this is not the exclusive indication for a video-EEG monitoring study. CONCLUSIONS: Nowadays, epilepsy surgery is not considered without a previous monitoring study. In this article we review the indications for a video-EEG monitoring must be included as an usual system of diagnosis in a Neurophysiology Unit.

[Surgical treatment of epilepsies: criteria for the selection of patients and results]. / Tratamiento quirúrgico de las epilepsias: criterios de selección de pacientes y resultados.

INTRODUCTION: Approximately 20% of all epileptic patients are not satisfactorily controlled by the available antiepileptic drugs. Some of these patients have epileptic syndromes which could potentially be treated by surgery. DEVELOPMENT: The technological advances applied to diagnostic and therapeutic methods have improved the identification of epileptic patients who may benefit from surgery. Up to 80% of the patients with focal epilepsies symptomatic of well defined lesions may become free of seizures after excision of the lesion or epileptogenic focus. Other forms of epilepsy, such as the so-called catastrophic infantile forms, may improve temporarily when techniques such as hemispherectomy or callosotomy are used. The morbidity and mortality of these surgical procedures are minimal. The results depend on correct selection of the patients. A strict protocol for rigorous evaluation of the patients should be used, with the collaboration of neurologists, epileptologist neuropaediatricians, neuropsychologists, neurophysiologists, neuroimaging specialists, psychiatrists and neurosurgeons. There should first be clear answers to three key questions: 1. Who is a good candidate? 2. How should the selection be made? and 3. When is the best time for evaluation? CONCLUSIONS: At present it seems clear that the surgery of epilepsy is used less than it could be. It is therefore necessary to encourage the development of specialist units to select patients and treat them, and to develop the means whereby patients can obtain this highly specialized attention.

[Postictal paralysis during video-EEG monitoring studies]. / Paresia poscrítica durante estudios de monitorización de vídeo-EEG.

OBJECTIVE: To know the frequency of Todd s paralysis during the video EEG monitoring studies, to investigate in its pathophysiology, and to confirm its value to localise the epileptic focus. PATIENTS AND METHODS: We reviewed 114 monitoring studies, in 102 patients. RESULTS: Sixty patients had epileptic seizures. An obvious paresis was noted in four seizures of two patients (3 and 1, respectively). Both patients had frontal epilepsy. During the paralysis, in the first patient the EEG showed ictal discharges on the contralateral centrotemporal area. In the second patient, the EEG demonstrated slow waves in the contralateral frontal region. The ictal onset was contralateral to the paresis in all cases. No patient with pseudoseizures had paralysis. CONCLUSIONS: Postconvulsive paralysis are not frequent in video EEG monitoring studies. However, if present it points out to a contralateral seizure onset. In our series it happened in patients with frontal seizures. The EEG may help to clarify if it correspond to a true postictal phenomenon or to a ictal paralysis.

[Safety of levetiracetam as adjunctive therapy in epilepsy: the SKATE trial in Spain]. / Seguridad del levetiracetam como tratamiento adyuvante en la epilepsia: el estudio SKATE en España.

AIM: To continue assessing safety and to evaluate the efficacy of levetiracetam and to assess the optimal dose in community based practice. PATIENTS AND METHODS: Single-arm, open label, multicenter, observational and prospective trial lasting 16-22 weeks. Criteria for inclusion: patients > 16 years experiencing epilepsy with partial seizures taking at least one concomitant antiepileptic drug. The initial dose was 1,000 mg/day, up to the maximal dose of 3,000 mg/day. Safety evaluation was adverse events reporting. Efficacy evaluation were reduction in seizure frequency; QOLIE-10 questionnaire and global evaluation scale of disease severity. RESULTS: Of the 342 subjects, 296 (86.5%) completed the treatment period. 103 subjects (30.1%) experienced at least one adverse event. The most frequently adverse events reported were somnolence (11.7%), dizziness (5.8%) and headache (3.5%). The events were majority (93.1%) of mild to moderate intensity. The median percent reduction in partial seizure frequency per week was 55%. 51.2% of patients experienced a reduction 50% in partial seizure frequency. Similar results were observed for total seizures. An increase of QOLIE-10 total score was observed (10.2 +/- 17.8). A total of 63.5% patients were rated as having moderate or marked improvement in their disease severity. CONCLUSIONS: These data confirm and provide additional support of levetiracetam safety and efficacy demonstrated in phase III trials.