bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on constitutions and physiology of skin‐development of traditional Chinese medicine for skin
Authors: Yokoi T. , Nakayama Y.
Published: November 2005

The Traditional Chinese Medicine (TCM) is considered medical treatment for constitutions (Shou). In women, who are healthy volunteers living in Tokyo, we investigated the relationship among the four types of skin condition and six types of constitution, which are based on the general idea of TCM. As a result, it is clear that skin types are composed of several constitutions. The constituent proportions of damp heat constitution and yin deficient constitution are high in the case of active skin (this type of skin tends to turn red and is easily partially inflamed). The constituent proportions of qi‐blood deficient constitution and yang deficient constitution are high in the case of inactive skin (this type of skin tends to be pale). The proportion of phlegm dampness constitution is high in the case of damp skin (this type of skin looks greasy and tends to break out in acne). The constituent proportions of qi‐blood deficient constitution and yin deficient constitution are high in the case of dry skin (this type of skin looks dry and rough). In other words, it is suggested that the features of the four types of skin are signified as the sum total of local symptoms composed of the constitutions. Furthermore, we trialled the external prescriptions of TCM, which changed the features of the four types of skin. It is proved that each of the external prescriptions of TCM can change the skin features according to the effective result of all of types of skin. Consequently, it is considered to be appropriate to classify skin type on the basis of TCM.
Study of sensory properties of emollients used in cosmetics and their correlation with physicochemical properties
Authors: Parente M. E. , Ga´ Mbaro A. , Solana G.
Published: November 2005

Eight liquid emollients (mineral oil, sunflower oil, squalane, decyl‐oleate, isopropyl‐myristate, octyldodecanol, dimethicone, and cyclomethicone) were characterized by instrumental and sensory methods and evaluated to determine the relationship between sensory and instrumental measures. Sensory analysis was carried out by a panel of 14 assessors, who evaluated the following attributes: difficulty of spreading, gloss, residue, stickiness, slipperiness, softness, and oiliness. The physicochemical properties measured were spreadability (at 1½ and 1 min), viscosity, and superficial tension. Data collected were statistically analysed by analysis of variance (ANOVA), principal component analysis (PCA), and linear partial least squares regression analysis (PLS). In consideration of their physicochemical characteristics, the studied emollients were sorted into three groups, in which the silicones distinctly separate from the rest. Sensory characteristics enabled the discrimination of four groups of emollients where, besides the two silicones, isopropyl myristate was also differentiated. PLS revealed that emollient sensory attributes could be well predicted by instrumental measurements.
Dissimilar effect of perming and bleaching treatments on cuticles: Advanced hair damage model based on elution and oxidation of S100A3 protein
Authors: Kizawa K. , Inoue T. , Yamaguchi M. , Kleinert P. , Troxler H. , Heizmann C. W. , Iwamoto Y.
Published: November 2005

Hair treatment chemicals induce sudden and severe hair damage. In this study, we examined cuticles from untreated, permed, and bleached hair that were mechanically discriminated by shaking in water. Both perming and bleaching treatments are prone to easily delaminate cuticles. Confocal microscopy revealed that the cuticles of permed hair were delaminated with larger pieces than untreated ones. On the other hand, the cuticles of bleached hair tend to fragment into small peptides. At the minimum concentration of thioglycolate required to elute S100A3 protein from the endocuticle into the reductive permanent waving lotion, enlarged delaminated cuticle fragments were observed. Although S100A3 is retained in bleached hair, S100A3 is irreversibly oxidized upon bleaching treatment. It is likely that the oxidative cleavage of disulfide bonds between cuticle‐constituting proteins, including S100A3, results in the fragile property of cuticles. Here we present a more comprehensive model of hair damage based on a diverse mechanism of cuticle delamination.
Hemp‐seed and olive oils: Their stability against oxidation and use in O/W emulsions
Authors: Sapino S. , Carlotti M. E. , Peira E. , Gallarate M.
Published: November 2005

Hemp‐seed oil has several positive effects on the skin: thanks to its unsaturated fatty acid (PUFA) content it alleviates skin problems such as dryness and those related to the aging process. We present a comparative study of hemp‐seed and olive oils, determining some physicochemical indices and evaluating their stability against oxidation. The peroxide value of hemp‐seed oil was below 20, the threshold limit for edible oils. Hemp‐seed oil was less stable against peroxidation than olive oil, but MDA and MONO assays showed its stability to be above expectations. The chlorophyll contained in extra virgin olive oil had a higher photostability than that contained in hemp‐seed oil, possibly due to the larger amount of antioxidant in the olive oil. A certain amount of Vitamin E was found in hemp‐seed oil. Since quality analyses indicated that hemp‐seed oil is relatively stable, emulsions were prepared with the two oils, and their stability and rheological characteristics were tested. Some of the resulting gel–emulsions were suitable for spraying on the skin.
Refractive index matching and clear emulsions
Authors: Ziming Sun J. , Erickson M. C. E. , Parr J. W.
Published: November 2005

Refractive index (RI) matching is a unique way of making clear emulsions to meet market trends. However, RI matching has not been sufficiently investigated in terms of physical principles and methodologies. Snell's law (n2 sin r2 = n1 sin r1) is applicable to cosmetic emulsions. When oil phase and water phase have equal RI (n2 = n1) values, light will not bend as it strikes obliquely at the emulsion interface. Instead, light is transmitted through the emulsion without refraction, which produces clarity. Theoretical RI values in solution can be calculated with summation of the product of the weight percentage and refractive index of each ingredient (RImix = [W1 × n1 + W2 × n2 + W3 × n3 + + Wn × nn]/WT). Oil‐phase RI values are normally at 1.4 or higher. Glycols are used to adjust the water phase RI, since they typically have larger RI values than water. Noticeable deviations from calculated RI values are seen in experimentally prepared solutions. Three basic deviation types are observed: negative, positive, and slightly negative or positive, which can occur in glycol aqueous solutions at different concentrations. The deviations are attributed to changes in molecular interaction between molecules in solution, which can lead to changes in specific gravity. Negative RI deviation corresponds to a decrease in specific gravity, and positive RI deviation corresponds to an increase in specific gravity. RI values will deviate from calculated values since an increase or decrease in specific gravity leads to a change in optical density.
Effects of age on human cumulative irritation responses
Authors: Bowman J., P. , Kligman A. M. , Stoudemayer T. , Nicholson J.
Published: November 2005

A 10‐day cumulative irritation test was conducted to evaluate whether or not test subjects 65 years of age and older would rank eleven test materials the same as subjects 18 to 45 years of age. The test materials consisted of mild to moderately irritating chemicals. The test articles were ranked similarly for both groups of subjects. Statistical analysis indicated no significant difference between the groups of subjects. Thus older subjects should not necessarily be excluded in comparative studies of irritancy.
Sexual differentiation in sensitivity to male body odor1
Authors: Tokunaga Y. , Omoto Y. , Sangu T. , Miyazaki M. , Kon R. , Takada K.
Published: November 2005

Synopsis

We have confirmed that more female subjects than male subjects evaluate male body odor as significantly unpleasant. Through an investigation on sexual differentiation in sensitivity to male body odor, we concluded that one of the volatile steroids, androstenone, had two effects on female olfactory sense. First, female subjects perceived androstenone itself to be more unpleasant than male subjects. Second, for only female subjects, androstenone, at a concentration of one‐tenth of detection threshold, enhanced the intensity and unpleasantness of body‐odor constituents such as short‐chain fatty acids.
Societal and Individual Determinants of Medical Care Utilization in the United States
Authors: ANDERSEN RONALD , NEWMAN JOHN F.
Published: November 2005

A theoretical framework for viewing health services utilization is presented, emphasizing the importance of the (1) characteristics of the health services delivery system, (2) changes in medical technology and social norms relating to the definition and treatment of illness, and (3) individual determinants of utilization. These three factors are specified within the context of their impact on the health care system. Empirical findings are discussed which demonstrate how the framework might be employed to explain some key patterns and trends in utilization. In addition, a method is suggested for evaluating the utility of various individual determinants of health services utilization used in the framework for achieving a situation of equitable distribution of health services in the United States.
Headache Prevention Outcome and Body Mass Index
Authors: Bigal ME , Gironda M , Tepper SJ , Feleppa M , Rapoport AM , Sheftell FD , Lipton RB
Published: November 2005

A population-based longitudinal study suggests that obesity is a strong risk factor for the development of headaches on 15 or more days per month. Little is know about the influence of weight on the response to headache preventive treatment. Herein we prospectively assessed the influence of the baseline body mass index (BMI) on the response to headache preventive treatment. We included adults with episodic or chronic migraine (ICHD-2), or transformed migraine (Silberstein and Lipton criteria) that sought care in a headache clinic. BMI was assessed in the first visit. Baseline information included headache frequency, number of days with severe headache (prospectively obtained over 1 month), and headache-related disability (HIT-6). The same information was obtained after 3 months of preventive treatment. Subjects were categorized based on BMI in: normal weight (≤24.9), overweight (25-29.9), or obese (≥30). We contrasted the headache end-points using ANOVA with post-test and Kruskal-Wallis with post-test. We used logistic regression to model BMI and headache parameters adjusting for covariates. Our sample consisted of 176 subjects (79.5% women, mean of 44.4 years). At baseline 40.9% had normal weight, 29.5% were overweight and 27.3% were obese. No significant differences were observed in the number of headache days at baseline. After treatment, frequency declined in the entire population, but no significant differences were found by BMI group. Regarding the number of days with severe pain per month, there were also no significant differences at baseline (normal = 6.1, overweight = 6.5, obese = 6.7), and improvement overall ( P = 0.01). However, changes were greater in the obese (reduction in 2.7 days with treatment) and overweight (3.9) vs. normal (1.5, P < 0.01). Finally, HIT scores at baseline did not differ by BMI group (normal weight = 63.8, overweight = 64.1, obese = 63.6). However, compared with the normal weighted group, change in HIT scores (followup baseline) were greater in the obese (6.4 vs. 3.5, P < 0.05) and overweight groups (6.8 vs. 3.5, P < 0.05). In the logistic regression model, BMI did not account for changes in disability, headache frequency, or in the number of days with severe headache per month, after adjusting for covariates. Contrary to what we hypothesized, obesity at baseline does not seem to be related to follow-up refractoriness to preventive treatment.
What is New About Idiopathic Intracranial Hypertension? An Updated Review of Mechanism and Treatment
Authors: Skau M , Brennum J , Gjerris F , Jensen R
Published: November 2005

Idiopathic intracranial hypertension (IIH) is the syndrome of raised intracranial pressure without clinical, laboratory or radiological evidence of intracranial pathology. IIH is a relatively rare disease but rapidly increasing incidence is reported due to a global increasing incidence of obesity. Disease course is generally said to be self-limiting within a few months. However, some patients experience a disabling condition of chronic severe headache and visual disturbances for years that limit their capacity to work. Permanent visual defects are serious and not infrequent complications. The pathophysiology of IIH is still not fully understood. Advances in neuroimaging techniques have facilitated the exclusion of associated conditions that may mimic IIH. No causal treatment is yet known for IIH and existing treatment is symptomatic and rarely sufficient. The aim of this review is to provide an updated overview of this potentially disabling disease which may show a future escalating incidence due to obesity. Theories of pathogenesis, diagnostic criteria and treatment strategies are discussed.
Counterfeiting of medicinal drugs: issues and threats
Authors: Juillet Yves , Vlasto Anne‐Priscille
Published: November 2005

The increasing counterfeiting of medicinal drugs is a very worrying phenomenon, especially in developing countries. The risk for public health is quite real, particularly as these products are often sold out of any controlled distribution channel.
The influence of weightlessness on pharmacokinetics
Authors: Gandia Peggy , Saivin Sylvie , Houin Georges
Published: November 2005

The primary hostile factor during a spaceflight is the lack of gravity, which can induce space motion sickness and act on bones, muscles and the cardiovascular system. These physiological effects may modify the pharmacokinetics of the drugs administered during the flight producing reduced pharmacological activity or appearance of adverse effects. Given the small number of spaceflights and the difficulties of conducting experiments during missions, pharmacokinetic data obtained in flight are insufficient to determine if drug monitoring is necessary for the drugs present in the onboard medical kit. Therefore, validated earthbound models like tail‐suspension performed with animals and long‐term bedrest performed with human volunteers are used to simulate weightlessness and to study the pharmacokinetic variations of either absorption, distribution, or elimination of drugs. As a result of these studies, it is possible to make some dosing recommendations but more information is necessary to predict with precision all of the pharmacokinetic variations occurring in spaceflight. To collect more pharmacokinetic information, head‐down bedrest studies are still the best solution and as saliva is an appropriate substitution for plasma for some drugs, salivary sampling can be planned during flights.
Chemopreventive efficacy and anti‐lipid peroxidative potential of Jasminum grandiflorum Linn. on 7,12‐dimethylbenz(a)anthracene‐induced rat mammary carcinogenesis
Authors: Kolanjiappan K. , Manoharan S.
Published: November 2005

The aim of this study was to investigate the chemopreventive efficacy and anti‐lipid peroxidative potential of Jasminum grandiflorum Linn. on 7,12‐dimethylbenz(a)anthracene (DMBA)‐induced rat mammary carcinogenesis. Mammary tumors were developed by a single subcutaneous injection of 25 mg DMBA in 1 mL emulsion of sunflower oil and physiological saline. The tumor incidence and tumor volume that formed in the breast were determined. Oral administration of ethanolic extract of J. grandiflorum flowers (JgEt) at a dose of 300 mg/kg body weight for 14 weeks to DMBA‐injected animals completely prevented the formation of tumors in the pre‐initiation period. JgEt also exerted significant anti‐lipid peroxidative effect and improved the antioxidant defense system in DMBA‐treated rats. The results of this study clearly indicate that JgEt has potent chemopreventive efficacy in experimental mammary carcinogenesis and further studies are warranted to isolate and characterize the bioactive principle from JgEt.
Cardiovascular and metabolic effects of natriuretic peptides
Authors: Moro Cédric , Berlan Michel
Published: November 2005

Natriuretic peptides (NP) are essential in mammals to regulate blood volume and pressure. The functional roles of NP are not limited to natriuresis and diuresis. Several peripheral and central actions of the peptides have been characterized. Studies on transgenic mice have revealed their key function in the regulation of cardiomyocyte growth. Plasma NP levels increase in patients with cardiovascular disorders and heart failure. They represent useful clinical markers for clinicians to diagnose heart diseases. The recent discovery of their potent lipolytic action in adipose tissue is a breakthrough in cardiovascular medicine. This new function of NP in the regulation of lipid metabolism offers interesting questions in the field of obesity, diabetes and cardiovascular diseases. This review will briefly describe the effects of NP on the cardiovascular system and lipid metabolism.
Lamotrigine pharmacokinetic/pharmacodynamic modelling in rats
Authors: Castel‐Branco M.M. , Falcão A.C. , Figueiredo I.V. , Caramona M.M.
Published: November 2005

The aim of this study was to perform a pharmacokinetic/pharmacodynamic (PK/PD) modelling of lamotrigine following its acute administration to rats. Adult male Wistar rats were given 10 mg/kg of lamotrigine intraperitoneally. Plasma and brain samples were obtained at predetermined times over 120 h post‐dose and analysed by liquid chromatography. The anticonvulsant profile against maximal electroshock seizure stimulation was determined over 48 h after dosing. As a linear relationship between lamotrigine plasma and brain profiles was observed, only the plasma data set was used to establish the PK/PD relationship. To fit the effect–time course of lamotrigine, the PK/PD simultaneous fitting link model was used: the pharmacokinetic parameters and dosing information were used in the one‐compartment first‐order model to predict concentrations, which were then used to model the pharmacodynamic data with the sigmoidEmaxmodel, in order to estimate all the parameters simultaneously. The following parameters were obtained:Vd = 2.00 L/kg,kabs = 8.50 h−1,kel = 0.025 h−1,ke0 = 3.75 h−1,Emax = 100.0% (fixed), EC50 = 3.44 mg/L andγ = 8.64. From these results, it can be stated that lamotrigine is extensively distributed through the body, its plasma elimination half‐life is around 28 h and a lamotrigine plasma concentration of 3.44 mg/L is enough to protect 50% of the animals. When compared with humans, the plasma concentrations achieved with this dose were within the therapeutic concentration range that had been proposed for epileptic patients. With the present PK/PD modelling it was possible to fit simultaneously the time‐courses of the plasma levels and the anticonvulsant effect of lamotrigine, providing information not only about the pharmacokinetics of lamotrigine in the rat but also about its anticonvulsant response over time. As this approach can be easily applied to other drugs, it becomes a useful tool for an explanatory comparison between lamotrigine and other antiepileptic drugs.
Radish seed extract mediates its cardiovascular inhibitory effects via muscarinic receptor activation
Authors: Ghayur Muhammad Nabeel , Gilani Anwarul Hassan
Published: November 2005

In this study, we describe the hypotensive, cardio‐modulatory and endothelium‐dependent vasodilator actions of Raphanus sativus (radish) seed crude extract in an attempt to provide scientific basis for its traditional use in hypertension. The plant extract (Rs.Cr) was prepared in distilled water and was subjected to phytochemical screening using standard analytical procedures. In vivo blood pressure was monitored in anaesthetized normotensive rats. Isolated tissue preparations were suspended in tissue baths containing Kreb's solution while acute toxicity study was performed in mice for 24 h. Rs.Cr tested positive for the presence of saponins, flavonoids, tannins, phenols and alkaloids and caused a dose‐dependent (0.1–3 mg/kg) fall in blood pressure and heart rate of rats that was mediated via an atropine‐sensitive pathway. In isolated guinea‐pig atria, Rs.Cr showed dose‐dependent (0.03–3.0 mg/mL) inhibition of force and rate of contractions. In the atropine‐treated tissues, the inhibitory effect was abolished and a cardiac stimulant effect was unmasked which was resistant to adrenergic and serotonergic receptor blockade. In the endothelium‐intact rat aorta, Rs.Cr inhibited phenylephrine‐induced contractions, which was blocked by atropine and Nω‐Nitro‐l‐arginine methyl ester hydrochloride while was also absent in the endothelium‐denuded preparations. The extract was safe in mice up to the dose of 10 g/kg. The study shows that the cardiovascular inhibitory effects of the plant are mediated through activation of muscarinic receptors thus possibly justifying its use in hypertension.
Differential caspase‐9‐dependent signaling pathway between tumor necrosis factor receptor‐ and Fas‐mediated hepatocyte apoptosis in mice
Authors: Imao Motohiro , Nagaki Masahito , Imose Motoaki , Moriwaki Hisataka
Published: November 2005

Abstract: Background/Aims: Two apoptosis signaling pathways, which are used by different cell types, are identified. The activation of caspases is critical for the apoptosis process. The aim of this study was to investigate the effects of the caspase‐9 inhibitor Ac‐LEHD‐CHO on tumor necrosis factor receptor (TNFR)‐ and Fas‐mediated hepatocyte apoptosis in vivo, in order to evaluate the similarities and distinctions between TNFR‐ and Fas‐mediated signaling pathways.

Methods: BALB/c mice were intravenously injected with d‐galactosamine (GalN, 20 mg/mouse)/tumor necrosis factor‐α (TNF‐α, 0.5 μg/mouse), or αFas (10 μg/mouse) 30 min after treatment with the caspase‐9 inhibitor Ac‐LEHD‐CHO or pan‐caspase inhibitor Z‐VAD‐fmk. Liver injury was assessed biochemically and histologically. Cytochrome c release and processing of procaspases in the liver were analyzed by Western blotting. Activities of caspases were measured using a fluorogenic peptide substrate.

Results: Pretreatment with Z‐VAD‐fmk prevented liver injury and hepatocyte apoptosis induced by either GalN/TNF‐α or αFas. On the other hand, pretreatment with Ac‐LEHD‐CHO prevented GalN/TNF‐α‐induced hepatotoxicity and hepatocyte apoptosis but not αFas‐induced liver injury and apoptosis. Both inhibitors reduced the activities of caspase‐9 and ‐3 in the livers of mice administered by GalN/TNF‐α. However, unlike Z‐VAD‐fmk, Ac‐LEHD‐CHO did not inhibit caspase‐3 activation in αFas‐treated mice, although this inhibitor attenuated caspase‐9.

Conclusion: Fas may rely on both caspase‐8 activation (extrinsic pathway) and mitochondria (intrinsic pathway) to activate caspase‐3. If the mitochondria‐dependent pathway is blocked, the other pathway can compensate. In contrast, TNFR may mediate hepatocellular apoptosis mainly through the mitochondria‐mediated caspase‐9 activation pathway alone.
Measurement of hepatitis B virus core‐related antigen is valuable for identifying patients who are at low risk of lamivudine resistance
Authors: Tanaka Eiji , Matsumoto Akihiro , Suzuki Fumitaka , Kobayashi Mariko , Mizokami Masashi , Tanaka Yasuhito , Okanoue Takeshi , Minami Masahito , Chayama Kazuaki , Imamura Michio , Yatsuhashi Hiroshi , Nagaoka Shinya , Yotsuyanagi Hiroshi , Kawata Sumio , Kimura Tatsuji , Maki Noboru , Iino Shiro , Kiyosawa Kendo ,   HBV Core‐Related Antigen Study Group
Published: November 2005

Abstract: Objective: The clinical usefulness of hepatitis B virus core‐related antigen (HBVcrAg) assay was compared with that of HBV DNA assay in predicting the occurrence of lamivudine resistance in patients with chronic hepatitis B.

Patients: Of a total of 81 patients who were treated with lamivudine, 25 (31%) developed lamivudine resistance during a median follow‐up period of 19.3 months.

Results: The pretreatment positive rate of HBe antigen, or pretreatment levels of HBVcrAg or HBV DNA did not differ between patients with and without lamivudine resistance. Levels of both HBVcrAg and HBV DNA decreased after the initiation of lamivudine administration; however, the level of HBVcrAg decreased significantly more slowly than that of HBV DNA. The occurrence of lamivudine resistance was significantly less frequent in the 56 patients whose HBV DNA level was less than 2.6 log copy/ml at 6 months of treatment than in the remaining 25 patients. The cumulative rate of lamivudine resistance was as high as 70% within 2 years in the latter group, while it was only 28% in the former group. Lamivudine resistance did not occur during the follow‐up period in the 19 patients whose HBVcrAg level was less than 4.6 log U/ml at 6 months of treatment, while it did occur in 50% of the remaining patients within 2 years.

Conclusion: These results suggest that measurement of HBV DNA is valuable for identifying patients who are at high risk of developing lamivudine resistance, and that, conversely, measurement of HBVcrAg is valuable for identifying those who are at low risk of lamivudine resistance.
Historical Aspects of Idiopathic Generalized Epilepsies
Authors: Wolf Peter
Published: November 2005

Summary:  Early in these proceedings, the origin of the three terms in the title, “idiopathic generalized epilepsy,” is discussed with respect to their significance over time, and typical misunderstandings. In the mid‐20th century, a rather chaotic use of a multitude of often loosely defined terms had developed, which increasingly became an obstacle to a meaningful international discussion. The International League against Epilepsy (ILAE) took the initiative to develop an internationally accepted terminology with a classification system consisting of a classification of seizures (1981) and a classification of syndromes (1989). The Idiopathic Generalized Epilepsies are one of its four major groups emerging from a double dichotomy of generalized versus localization‐related and idiopathic versus symptomatic.

The inclusion of biologic aspects such as syndrome‐specific ages of onset (“age‐related syndromes”) or syndrome‐specific relations of seizure occurrence to the sleep–wake cycle (“Epilepsy with Grand Mal on Awaking”) meant that the syndrome classification merged the more biological views of the German school with the more neurophysiological ones of the French.

Apart from establishing a common international language concerning epilepsy, the International Classification of Epilepsies and Epileptic Syndromes became an important stimulator of research, especially concerning the idiopathic epilepsies. In particular, genetic and functional imaging investigations aim at a better understanding of these conditions. It is now understood that most idiopathic syndromes have a—sometimes complex—genetic background, but we are also becoming aware of the inappropriateness of the time‐honored term “generalized” and part of our dichotomies. Both localization‐related and “generalized” idiopathic epilepsies seem to share a principle of ictogenesis based on functional anatomic pathogenic networks, and we seem to move toward understanding them as functional system disorders of the brain.
Cellular and Network Mechanisms of Spike‐Wave Seizures
Authors: Blumenfeld Hal
Published: November 2005

Summary:  Spike‐wave seizures are often considered a relatively “pure” form of epilepsy, with a uniform defect present in all patients and involvement of the whole brain homogenously. Here, we present evidence against these common misconceptions. Rather than a uniform disorder, spike‐wave rhythms arise from the normal inherent network properties of brain excitatory and inhibitory circuits, where they can be provoked by many different insults in several different brain networks. Here we discuss several different cellular and molecular mechanisms that may contribute to the generation of spike‐wave seizures, particularly in idiopathic generalized epilepsy. In addition, we discuss growing evidence that electrical, neuroimaging, and molecular changes in spike‐wave seizures do not involve the entire brain homogenously. Rather, spike‐wave discharges occur selectively in some thalamocortical networks, while sparing others. It is hoped that improved understanding of the heterogeneous defects and selective brain regions involved will ultimately lead to more effective treatments for spike‐wave seizures.
Seizures of Idiopathic Generalized Epilepsies
Authors: Durón Reyna M. , Medina Marco T. , Martínez‐Juárez Iris E. , Bailey Julia N. , Perez‐Gosiengfiao Katerina Tanya , Ramos‐Ramírez Ricardo , López‐Ruiz Minerva , Alonso María Elisa , Ortega Ramón H. Castro , Pascual‐Castroviejo Ignacio , Machado‐Salas Jesús , Mija Lizardo , Delgado‐Escueta Antonio V.
Published: November 2005

Summary:  Idiopathic generalized epilepsies (IGEs) comprise at least 40% of epilepsies in the United States, 20% in Mexico, and 8% in Central America. Here, we review seizure phenotypes across IGE syndromes, their response to treatment and advances in molecular genetics that influence nosology. Our review included the Medline database from 1945 to 2005 and our prospectively collected Genetic Epilepsy Studies (GENESS) Consortium database. Generalized seizures occur with different and similar semiologies, frequencies, and patterns, ages at onset, and outcomes in different IGEs, suggesting common neuroanatomical pathways for seizure phenotypes. However, the same seizure phenotypes respond differently to the same treatments in different IGEs, suggesting different molecular defects across syndromes. De novo mutations in SCN1A in sporadic Dravet syndrome and germline mutations in SCN1A, SCN1B, and SCN2A in generalized epilepsies with febrile seizures plus have unraveled the heterogenous myoclonic epilepsies of infancy and early childhood. Mutations in GABRA1, GABRG2, and GABRB3 are associated with absence seizures, while mutations in CLCN2 and myoclonin/EFHC1 substantiate juvenile myoclonic epilepsy as a clinical entity. Refined understanding of seizure phenotypes, their semiology, frequencies, and patterns together with the identification of molecular lesions in IGEs continue to accelerate the development of molecular epileptology.
Status Epilepticus in Idiopathic Generalized Epilepsy
Authors: Shorvon Simon , Walker Matthew
Published: November 2005

Summary:  Status epilepticus (SE) can take various forms in idiopathic generalized epilepsy (IGE), some of which forms also occur in symptomatic or focal epilepsies. Although the clinical semiology of the SE episodes may be similar in these different epilepsies, the frequency, response to treatment and prognosis differ. (a) Convulsive SE is surprisingly uncommon in IGE and much less common than in the secondarily generalized or partial epilepsies. Also, when it does occur, it usually responds rapidly to treatment. (b) Typical absence SE occurs only in patients with IGE (the subcategories with typical absence seizures) and also in the syndrome of de novo absence SE of late onset. This form of nonconvulsive SE should be differentiated from atypical absence SE, which occurs in the secondarily generalized epilepsy encephalopathies, and from complex partial SE which occurs in focal epilepsy. The clinical symptoms of these three types overlap but the prognosis and response to treatment are different. The mechanisms underlying absence SE are uncertain and may include both genetic and environmental factors. The termination of absence seizures has been hypothesized to be due to persistent activation of a depolarizing current in thalamocortical neurons that inactivates T‐type calcium channels. SE could thus result from dysfunction of this channel or mechanisms that hyperpolarize thalamocortical neurons—these include decreased cortical inhibition, increased reticular thalamic neuronal activity or increased thalamocortical neuron GABAB‐receptor activation. (c) Generalized electrographic SE is encountered in IGE in the syndrome of phantom absence with GTCS. It also occurs in ESES and in the Landau–Kleffner syndrome. The seizure phenomenology overlaps with the focal SE of temporal or frontal lobe epilepsy. (d) Myoclonic SE is also uncommon in IGE but occurs in juvenile myoclonic epilepsy. It is more commonly encountered in progressive myoclonic epilepsies, myoclonic‐astatic epilepsy and in the Dravet syndrome. (e) Autonomic status occurs largely in the Panayiotopoulos syndrome. It is included here under the rubric of IGE, although the epilepsy has focal as well as generalized features and its nosological position is controversial. Fifty percent of seizures in this syndrome could be classified as status epilepticus. There is no doubt that convulsive SE can result in cerebral damage. In animal models of focal SE, nonconvulsive forms can also result in cerebral damage, but cerebral damage is not observed in animal models of absence SE. Similarly, cerebral damage seems not to occur in the forms of nonconvulsive SE in human IGE.
Nonepileptic Disorders Imitating Generalized Idiopathic Epilepsies
Authors: Fejerman Natalio
Published: November 2005

Summary: Differential diagnosis between epileptic and nonepileptic paroxysmal disorders is fundamental not only to allow correct management of patients but also to avoid the burden of unnecessary antiepileptic medication. The focus of this chapter is limited to imitators of idiopathic generalized epilepsies (IGE) which are expressed through myoclonic, tonic–clonic, tonic, atonic, and absence seizures. Apparent losses of consciousness and drop attacks also have to be considered. Benign myoclonus of early infancy is the main nonepileptic disorder in the differential diagnosis of infantile spasms, but is not dealt with here because West syndrome is not an IGE. Hyperekplexia, metabolic disorders, hypnagogic myoclonus, and disturbed responsiveness caused by the use of drugs are listed inTable 1. Other conditions that may imitate more focal epileptic seizures are omitted. Benign neonatal sleep myoclonus, apnea and apparent life‐threatening events in infants, cyanotic and pallid breath‐holding spells, syncope, staring spells, psychogenic seizures, hyperventilation syndrome, and narcolepsy have been selected based on frequency or difficulties in differential diagnosis with the intention to cover the most conspicuous imitators of IGE in different ages.

Nonepileptic disorders imitating idiopathic generalized epilepsies

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Symptomatic Epilepsies Imitating Idiopathic Generalized Epilepsies
Authors: Oguni Hirokazu
Published: November 2005

Summary:  The diagnosis of idiopathic generalized epilepsies (IGEs) is not generally difficult if one follows the clinical and electroencephalogram (EEG) definitions of each subsyndrome that constitutes IGEs. In contrast, symptomatic epilepsies develop based on organic brain lesions and are easily diagnosed by the presence of developmental delay, neurologic abnormalities, and a characteristic seizure and EEG pattern. However, in clinical practice, it is sometimes difficult to differentiate IGEs from symptomatic epilepsies, especially when the clinical course from the onset of epilepsy is too short to exhibit typical clinical and EEG findings of either epilepsy type, or when patients with symptomatic epilepsies have atypical features that imitate the clinical characteristics of IGEs. The neurodegenerative or metabolic disorders at times start during the clinical course with epileptic seizures and later show typical neurologic abnormalities. The newly recognized metabolic disorder of glucose transporter type 1 deficiency syndrome (Glut‐1 DS) may start with myoclonic seizures at an age of less than 1 year and imitate benign myoclonic epilepsy in infancy early in the clinical course. Progressive myoclonus epilepsies (PMEs) that develop at 1–4 years of age at times imitate epilepsy with myoclonic‐astatic seizures with respect to the presence of astatic seizures and an epileptic encephalopathic EEG pattern. In addition, young children with focal cortical dysplasia may also have similar clinical and EEG patterns, although the latter may become localized after treatment. Approximately 15% of patients with juvenile myoclonic epilepsy (JME) are resistant to antiepileptic drugs (AEDs) and may require extensive study to make a differential diagnosis from symptomatic epilepsies. PMEs that develop during adolescence may imitate JME early in the clinical course; however, a detailed history and the differentiation between myoclonic seizures and myoclonus would help to distinguish both conditions. The diagnosis of IGEs is very demanding for patients with atypical features with regard to seizure type, EEG findings, and response to appropriate AEDs.
Idiopathic Generalized Epilepsies Imitating Focal Epilepsies
Authors: Ferrie Colin D.
Published: November 2005

Summary:  Classification of epileptic seizures and epilepsy syndromes as either focal or generalized is a fundamental and early part in the diagnostic process and is generally fairly easily accomplished. However, in patients with idiopathic generalized epilepsies, seizure and EEG features may suggest, particularly to the unwary, the occurrence of focal rather than generalized seizures. Misinterpretation of typical absence seizures as focal seizures, especially as temporal lobe seizures and of myoclonic seizures as focal clonic seizures, is a relatively common error and focal features during generalized tonic–clonic seizures may also be quite common. Sequences of seizures in idiopathic generalized epilepsies (such as absences or jerks followed by generalized tonic–clonic seizures) may also cause confusion. Versive and circling seizures are seizure types whose ictal semiology is clearly focal; nevertheless such seizures are described in idiopathic generalized epilepsies accompanied by generalized EEG discharges. The occurrence of focal EEG abnormalities in certain idiopathic generalized epilepsy syndromes is common. This is best known in juvenile myoclonic epilepsy.
Use and Abuse of EEG in the Diagnosis of Idiopathic Generalized Epilepsies
Authors: Koutroumanidis Michael , Smith Shelagh
Published: November 2005

Summary: This article concentrates on the role of electroencephalograms (EEGs) in the diagnosis and management of patients with idiopathic generalized epilepsies (IGEs). We review the morphologic and behavioral characteristics of the interictal and ictal EEG markers of IGE that should guide recording strategies to augment its diagnostic yield, and we attempt to delineate those particular features that may be relevant to different IGE syndromes. We also explore the electrographic boundaries between IGEs and cryptogenic/symptomatic generalized and focal epilepsies, and focal/secondary generalized epilepsies, with particular relevance to the phenomena of focal abnormalities and secondary bilateral synchrony, commenting on possible diagnostic pitfalls and areas of uncertainty.
Management Guidelines for Children with Idiopathic Generalized Epilepsy
Authors: Camfield Carol , Camfield Peter
Published: November 2005

Summary:  Most idiopathic generalized epilepsy (IGE) begins in childhood. Clinicians face many important management decisions for these children; however the existing literature provides little scientific guidance.

Time of Diagnosis: At the time of presentation, it is unclear how accurately IGE seizures and syndromes are diagnosed and how consistent are the EEG correlates. Investigations beyond EEG are of uncertain value but probably are not needed. Selection of an initial antiepileptic drug (AED) is not based on any adequately powered, blinded, randomized comparative trials; however, reasonable evidence supports the use of valproic acid (VPA), lamotrigine and ethosuccimide as initial treatment for childhood absence epilepsy (CAE). Many large case series suggest the value of VPA for juvenile myoclonic epilepsy (JME) but the relative value of other, newer AEDs has not been established.

First years of treatment: Once AED treatment is started, it is difficult to establish that absence seizures are completely controlled and the importance of interictal spike‐wave discharge remains uncertain. The value of restrictions on the child's activities has not been well studied; however serious accidents appear to be a justifiable concern in children with uncontrolled absence. Assessing the risk from photosensitivity in JME is challenging.

Length of treatment: The optimal length of treatment for IGE is unclear. There is a high rate of remission in CAE when AEDs are discontinued after 1–2 years of seizure freedom; however, long‐term remission in CAE occurs in only 65%. It is usually assumed that treatment for JME is life long, although about 10% appear to have permanent remission in adolescence. Discontinuing AED treatment in JME requires a very individual risk assessment.

Preparation for adult life: Long‐term social outcome for children with CAE is often unsatisfactory even if the epilepsy remits. The reasons are unclear and successful interventions have not been described. Long‐term social outcome for JME has not been adequately described.

Conclusions: Further research is needed to justify the direction of many of the necessary management decisions in the diagnosis and treatment of IGE syndromes.
Practical Management Issues for Idiopathic Generalized Epilepsies
Authors: Benbadis Selim R.
Published: November 2005

Summary: The idiopathic generalized epilepsies (IGE) are a group of epilepsies that are genetically determined, have no structural or anatomic cause, and usually begin early in life. Neurologic examination, intelligence, and imaging studies are normal, and EEG shows only epileptiform abnormalities (i.e., no abnormal slow activity or evidence for diffuse encephalopathy). In some IGE, the genetic substrate has been identified, whereas in most, it remains unknown. Depending on the age at onset and predominant seizure type, individual subtypes of IGE (syndromes) are defined. However, overall, there are more similarities than there are differences among the various subtypes, and the IGE are best viewed as a spectrum or continuum of conditions. In general, IGE respond to treatment, with 80–90% becoming fully controlled. However, not all antiepileptic drugs (AED) are equally effective in IGE. Some AED are ill advised because they either do not work or exacerbate seizure types other than generalized tonic–clonic (GTC) seizures, that is, absence and myoclonic seizures. These include carbamazepine, oxcarbazepine, phenytoin, gabapentin, and tiagabine. Their use is the main cause of “pseudo‐intractability,” and at least in the United States where PHT and CBZ are the most commonly used AEDs, patients with IGE are often on inadequate medications. For patients with clear IGE, the drug of choice is generally valproic acid because it effectively controls absence myoclonic seizures and GTC seizures. Second‐line drugs (when first‐line drugs fail or are not tolerated) may include benzodiazepines, but the use of second‐line drugs is evolving rapidly. Some of the newer AEDs are considered broad spectrum, meaning that they work in IGE and focal epilepsies, although the evidence is largely preliminary at this point. These newer AEDs include lamotrigine, topiramate, levetiracetam, and zonisamide.
Evidence‐based Treatment of Idiopathic Generalized Epilepsies with New Antiepileptic Drugs
Authors: Bergey Gregory K.
Published: November 2005

Summary:  With the introduction of over ten new antiepileptic drugs (AEDs) since 1993, the hope has been that at least some of these agents would be useful for not just partial seizures, but also for the primary generalized seizures of the idiopathic generalized epilepsies (IGE). The development of evidence‐based treatment guidelines in the IGE, however, faces a number of challenges, particularly after an antiepileptic drug (AED) receives approval for one indication. The majority of patients with IGE are controlled with first‐line therapy if appropriately selected. Case reports or series typically appear with use in refractory patients, but these studies lack the rigor to allow formulation of guidelines. Still we are beginning to see some good class I and II data to support use of selected second‐generation AEDs. It is postulated that lamotrigine (LTG), levetiracetam (LEV), topiramate (TPM), and zonisamide (ZSM) may have efficacy for a broad spectrum of seizure types including those of IGE. At the present time good class I and II evidence exists to support the use of LTG for typical absence, LEV for idiopathic myoclonic seizures, and TPM for primary generalized tonic–clonic seizures, even though only TPM has FDA approval for primary generalized seizures. This article examines the available rigorous evidence that can support these uses and also discusses some selected other reports that suggest a spectrum of efficacy for these new agents.
Levetiracetam in the Treatment of Idiopathic Generalized Epilepsies
Authors: Grünewald Richard
Published: November 2005

Summary: Since its introduction into clinical practice in 1999, levetiracetam, the S enantiomer of piracetam, has rapidly found a secure place, initially in the therapy of partial onset seizures and subsequently in the treatment of idiopathic generalized epilepsies (IGE). It has many of the properties of an “ideal” antiepileptic drug, including rapid absorption, linear pharmokinetics, and sparse drug interactions. Tolerabiliy is generally excellent in both adults and children, although tiredness is a common dose‐limiting adverse effect. Occasionally the drug can precipitate behavioral abnormalities, especially in patients with learning disability. There is a wide safety margin in overdose. In common with most antiepileptic drugs its mode of action remains uncertain. Levetiracetam binds to a specific site in the brain, influences intracellular calcium currents and reverses negative allosteric modulators of GABA‐ and glycine‐gated currents in vitro. Its effectiveness has been demonstrated in animal models of epilepsy and in clinical trials of partial onset and IGE. Treatment of IGEs may be straightforward, with many patients demonstrating an excellent and robust response to valproate monotherapy. However, there remains a significant minority of patients for whom valproate is unsuitable, including those who experience unacceptable adverse effects (e.g., weight gain or hair loss) and women of childbearing age in whom the teratogenic potential of valproate is unacceptable. Therapeutic response to lamotrigine in this group is often disappointing, and many clinicians now are turning to the choice of levetiracetam. Efficacy in generalized tonic–clonic seizures and myoclonus is usually apparent and some patients experience improvement in typical absences. Experience of combinations of levetiracetam with other antiepileptic drugs is limited in IGE and the responses are largely anecdotal. In our hands, patients with refractory IGEs may respond to combinations of levetiracetam with valproate, lamotrigine, and phenobarbital, and adverse effects when they occur are usually limited to tiredness. Levetiracetam does not interact with the oral contraceptive pill, simplifying treatment in women of childbearing age. Although animal data look encouraging, questions over levetiracetam's teratogenic potential and overall safety in pregnancy will remain for many years to come.