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Apuntes en Neurologia is an initiative in which prominent national and international leaders, with broad academic recognition, came together to synthesise the most outstanding clinical aspects within their area of interest and to discuss the latest developments in a more accessible language. Understanding the factors that affect the onset and progression of any neurological disease through a review is important to be able to develop strategies to reduce the burden of these diseases. Moreover, knowledge of the clinical aspects is essential to solve the problems of daily clinical practice. The data collected here reflect the weight of evidence and some of them anticipate a promising future in the treatment of these diseases. This first edition focuses on common paroxysmal neurological disorders such as migraine, epilepsy and sleep disorders, as well as neurodegenerative disorders such as Parkinson's disease and cognitive impairment. These are clearly different pathologies, although some of them such as migraine and epilepsy, may share clinical symptoms. Sleep disorders, however, are important manifestations of neurodegenerative diseases that are sometimes clinically apparent long before the onset of other neurological symptoms. After recalling pathophysiology and diagnosis, the current review focuses on bringing together the main advances in five of the major neurological diseases. TITLE: Apuntes en Neurologia: una sintesis de la evidencia en trastornos neurologicos comunes paroxisticos y en trastornos neurodegenerativos. Apuntes en Neurologia es una iniciativa en la cual lideres de primera linea nacional e internacional, con amplio reconocimiento academico, se reunieron para sintetizar los aspectos clinicos mas destacables dentro de su area de interes y acercar las novedades en una lengua mas proxima. Entender los factores que afectan al inicio y progresion de cualquier enfermedad neurologica a traves de una revision es importante para el desarrollo de estrategias en pro de reducir la carga de estas enfermedades, y conocer los aspectos clinicos es esencial para poder resolver los problemas de la practica clinica diaria. Los datos aqui recogidos reflejan el peso de la evidencia y algunos de ellos anticipan un futuro prometedor en el tratamiento de estas enfermedades. Esta primera edicion se centra en trastornos neurologicos comunes paroxisticos como la migrana, la epilepsia y las alteraciones del sueno, y en trastornos neurodegenerativos como la enfermedad de Parkinson y el deterioro cognitivo. Se trata de patologias claramente diferentes, si bien algunas de ellas, como la migrana y la epilepsia, pueden compartir sintomatologia clinica. Los trastornos del sueno, por su parte, son manifestaciones importantes de enfermedades neurodegenerativas que, en ocasiones, son clinicamente evidentes mucho antes del inicio de otros sintomas neurologicos. Tras recordar la fisiopatologia y el diagnostico, la revision actual se centra en acercar los principales avances en cinco de las principales enfermedades neurologicas.

D'apres Mackor, la variation du point de charge nulle des suspensions colloidales de AgI dans les melanges eau-acetone est du tout d'abord au saut brusque du potentiel x de Lange aux faibles concentrations en acetone, et ensuite, a la variation de l'enthalpie libre de solvatation de l'ion Ag+ aux plus fortes teneurs en acetone. Utilisant la methode microelectrophoretique a fond noir, nous trouvons pour AgI et AgBr un saut du potentiel x de 225 mV et pour AgCl un saut de 105 mV. Toutefois, la variation de l'enthalpie libre de solvatation de l'ion Ag+ pour les trois types de suspensions colloidales est identique, ce qui verifie parfaitement l'hypothese de Mackor.

Ohtahara syndrome (OS, OMIM#308350, ORPHA1934) is an early-onset epileptic encephalopathy (EOEE) characterised by spasms, intractable seizures, suppression-burst pattern on the electroencephalogram, and severe psychomotor retardation. Mutations in STXBP1 -a gene that codes for syntaxin binding protein 1 and is involved in synaptic vesicle exocytosis- has been identified in most patients with OS.We report the case of a 19-month-old child with OS who displays a previously unreported mutation in STXBP1 (c.1249+2TC, G417AfsX7). This mutation is located in a donor splice site and eliminates exon 14, resulting in a truncated protein.This previously unreported STXBP1 mutation in a subject with Ohtahara syndrome and non-lesional magnetic resonance imaging (MRI) broadens the mutational spectrum associated with this devastating epileptic syndrome.

The alkali treatment of kaolinites heated between 400 and 1,000{degree}C has been studied by NMR ({sup 29}Si and {sup 27}Al signals), IR, and x-ray diffraction techniques. The dissolution of kaolinite samples produces Al(OH){sub 4}{sup {minus}} and SiO{sub 4}{sup 4{minus}} species which participate in the zeolite germ formation. The nature of zeolites generated (hydroxysodalite, Na-A, and tetragonal P{sub t}) varies with thermal activation of the starting silicates, but the prolonged leaching of the samples favors the transformation of initially formed phases into the most stable P{sub t} zeolite. The synthesis of this compound (Si/Al > 1) requires the previous polymerization of dissolved silica species, and the amount of incorporated Si depends on the temperature of pretreatment of kaolinite.

The arrangement of water molecules in one- and two-layer hydrates of high-charged vermiculites, saturated with alkaline (Li(+), Na(+)) and alkali-earth (Mg(2+), Ca(2+), Ba(2+)) cations, has been analyzed with (1)H NMR spectroscopy. Two different orientations for water molecules have been found, depending on the hydration state and the sites occupied by interlayer cations. As the amount of water increases, hydrogen bond interactions between water molecules increase at expenses of water-silicate interactions. This interaction favors water mobility in vermiculites. A comparison of the temperature dependence of relaxation times T(1) and T(2) for one and two-layer hydrates of Na-vermiculite shows that the rotations of water molecules around C(2)-axes and that of cation hydration shells around the c-axis is favored in the two-layer hydrate. In both hydrates, the anisotropic diffusion of water takes place at room temperature, preserving the orientation of water molecules relative to the silicate layers. Information obtained by NMR spectroscopy is compatible with that deduced by infrared spectroscopy and with structural studies carried out with X-ray and neutron diffraction techniques on single-crystals of vermiculite.

To continue assessing safety and to evaluate the efficacy of levetiracetam and to assess the optimal dose in community based practice.Single-arm, open label, multicenter, observational and prospective trial lasting 16-22 weeks. Criteria for inclusion: patients16 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.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.These data confirm and provide additional support of levetiracetam safety and efficacy demonstrated in phase III trials.

Catastrophic epilepsy is a term applied to epilepsies with early onset, frequent and refractory seizures and cognitive impairment. The prognosis of these epilepsies is usually unfavorable. However, only a suitable diagnosis will allow the right treatment and a better prognosis.At the time of this writing there are a wide range of diagnostic tests, such as RMI, PET and video EEG that may lead right diagnostic of patients.The spectrum of therapies has also been widened. New antiepileptic drugs, with new mechanisms of action are being developed as well as improved surgical techniques. The rational use of these procedures will optimize control of seizures and improve cognitive impairment.

The recent and increasing interest for previously undescribed forms of epilepsy has been due to the description of families in which several affected members presented specific forms of epilepsy. Most epilepsies representing the description of new epilepsy phenotypes are partial epilepsies, although a new form of generalized epilepsy (generalized epilepsy with febrile seizures plus or GEFS+) has also been described. Our understanding of the clinical and genetic characteristics of the new familial epilepsy syndromes and the identification of informative families should accelerate the discovery of the basic mechanisms implicated in the production of partial seizures. The recent description of the syndrome of autosomal dominant nocturnal frontal lobe epilepsy, its localization to chromosome 20, the identification of the responsible gene (the alpha 4 subunit of the nicotinic cholinergic receptor) and the characterization of a mutation in two families are a good example. The recognition of the new epilepsy syndromes is of great interest for clinical neurologists and should lead to the establishment of more precise prognoses and therapies. In those families with several affected members, genetic knowledge may be important for genetic counseling purposes.

Recent advances in mapping and isolating human epilepsy genes are having an increasing importance in the field of epileptology.As the molecular bases of the genetic epilepsies are elucidated, more precise diagnoses and therapies are possible. Characterization of the genes responsible for several types of epilepsy will allow the clinician to increase diagnostic precision, offer more exact prognoses, and develop more efficient therapies. At the same time, the search for families with several affected members with some form of epilepsy has lead to the description of previously unnoticed epilepsies and epileptic syndromes. Both the precision in diagnosis and the description of new epilepsy syndromes should be of major importance for the development of the next version of the International Classification of Epilepsies and Epileptic Syndromes. Understanding the pathogenic mechanisms involved in different epilepsies may allow the rational development of 'design' antiepileptic drugs and, in the case of the poor-prognosis progressive myoclonus epilepsies, effective gene therapy treatments. Finally, the possibility of offering prenatal diagnosis and genetic counseling to families exposed to some forms of epilepsy may reduce their incidence in the future.

In 1995, we mapped a gene for Lafora's progressive myoclonus epilepsy in chromosome 6q23-25. In 1997 and 1998, we reduced the size of the locus to 300 kb, and an international collaboration identified mutations in the protein tyrosine phosphatase gene. Here, we examine for heterogeneity through the admixture test in 22 families and estimate the proportion of linked families to be 75 to 85%. Extremely low posterior probabilities of linkage (Wi), exclusionary LOD scores, and haplotypes identify 4 families unlikely to be linked to chromosome 6q24.

Until recently, research in the field of genetics of the epilepsies had mainly focused on the idiopathic generalized epilepsies and the progressive myoclonic epilepsies. Interest in the genetics of the partial epilepsies has now increased due to the identification of several forms of partial epilepsies with a strong genetic component. The genetic partial epilepsies appear to be more common than expected and each description of a new syndrome is followed by reports of more patients and families. Understanding the clinical and genetic characteristics of the new familial partial epilepsy syndromes and identifying informative families will accelerate the discovery of the basic mechanisms implicated in the production of partial seizures. The recent description of the syndrome of autosomal dominant nocturnal frontal lobe epilepsy, its localization to chromosome 20, and the identification of the responsible gene and mutation in the alpha 4 subunit of the nicotinic cholinergic receptor in an Australian family are a good example. Future discoveries in the genetics of the partial epilepsies will have important diagnostic, prognostic and therapeutic implications and will allow us to apply more specific treatments for each syndrome, offer a prognosis to patients and develop novel forms of therapy.

We recently analyzed under homogeneity a large pedigree from Belize with classic juvenile myoclonic epilepsy (JME). After a genome wide search with 146 microsatellites, we obtained significant linkage between chromosome 6p markers, D6S257 and D6S272, and both convulsive and EEG traits of JME. Recombinations in two affected members defined a 40 cM JME region flanked by D6S313 and D6S258. In the present communication, we explored if the same chromosome 6p11 microsatellites also have a role in JME mixed with pyknoleptic absences. We allowed for heterogeneity during linkage analyses. We tested for heterogeneity by the admixture test and looked for more recombinations. D6S272, D6S466, D6S294, and D6S257 were significantly linked (Zmax3.5) to the clinical and EEG traits of 22 families, assuming autosomal dominant inheritance with 70% penetrance. Pairwise Zmax were 4.230 for D6S294 (theta m = f at 0.133) and 4.442 for D6S466 (theta m = f at 0.111). Admixture test (H2 vs. H1) was significant (P = 0.0234 for D6S294 and 0.0128 for D6S272) supporting the hypotheses of linkage with heterogeneity. Estimated proportion of linked families, alpha, was 0.50 (95% confidence interval 0.05-0.99) for D6S294 and D6S272. Multipoint analyses and recombinations in three new families narrowed the JME locus to a 7 cM interval flanked by D6S272 and D6S257.

Progressive myoclonus epilepsy of the Lafora type (Lafora's disease) is an autosomal recessive disease characterized by epilepsy, myoclonus, dementia, and periodic acid-Schiff-positive intracellular inclusion bodies. The inclusion deposits consist of branched polysaccharides (polyglucosans) but the responsible biochemical defect has not been identified. Onset is during late childhood or adolescence and the disease leads to a fatal outcome within a decade of first symptoms. We studied nine families in which Lafora's disease had been proven by biopsy in at least one member. In order to locate the responsible gene, we screened the human genome with microsatellite markers spaced an average of 13 cM. We used linkage analysis in all nine families and homozygosity mapping in four consanguineous families to define the Lafora's disease gene region. Two point linkage analysis resulted in a total peak lod score of 10.54 for marker D6S311. Six additional chromosome 6q23-25 microsatellites yielded lod scores ranging from 5.92 to 9.60 at theta m = f = 0. An extended pedigree with five affected members independently proved linkage with peak lod scores over 3.8 at theta m = f = 0 for D6S292, D6S403, and D6S311. The multipoint one-lod-unit support interval covered a 2.5 cM region surrounding D6S403. Homozygosity mapping defined a 17 cM region in chromosome 6q23-25 flanked by D6S292 and D6S420 that contains the Lafora's disease gene.

Fibrous sepiolite crystals derive much of their commercial value from their molecular size channels and grooves. The crystals fold upon drying and these channels and grooves are lost. A model for the folding and unfolding of the crystals is presented. Extensive i.r., X-ray and thermogravi- metric evidence shows that folding occurs when approximately half of the water of hydration, which is coordinated to the edge magnesium atoms inside of the channels, is removed. This occurs near 175~ under vacuum and near 300~ in air. When the crystals fold, all remaining water molecules enter a new environment, that of the hexagonal holes of the neighboring silica surface. A true anhydride is produced at about 500~ under vacuum when the final water is lost, but this final dehydration produces no important structural change. Rehydration of the anhydride to the normal hydrated sepiolite does not occur at room temperatures in 100% r.h. However, above, 60~ rehydration does occur. not after the high temperature treatment. Nagata et al. (1974) consider that the folded stage produced at half dehydration will rehydrate, but the true anhy- dride does not rehydrate even under hydrothermal conditions, Our study is designed to clarify the conditions un- der which sepiolite folds and unfolds and the involve- ment of the water of coordination in the folding. In- terpretation of TGA-DTGA. X-ray powder diffrac- tion patterns and, especially, careful study of the major changes observable in the i.r. spectra of the struc- tural OH during the dehydration and folding process will be used to explain a folding model.

29Si MAS-NMR spectra were obtained for vermiculite with tetrahedral composition x=Al/(Al+Si)=0.28, a synthetic mica with x=0.43, and margarite with x=0.5. Comparison between the observed and Monte-Carlo simulated spectra was used to test different Al-Si distribution schemes in the tetrahedral sheet. The results of this analysis are interpreted including earlier data corresponding to lower Al for Si substitutions (0.12≤x≤0.28), and it is shown that for all samples (8 compositions in the range 0.1≤x≤0.5) the Al-Si distribution complies with the principle of homogeneous dispersion of charges (HDC). Thus, Al-Si distribution models for any particular x can be predicted on the basis of a simple crystallochemical criterion. HDC is a short range order concept and implies that, within the restrictions imposed by the principle, charges be distributed at random. For increasing values of x, however, the observance of HDC implies a coupling between adjacent hexamer rings which restricts the degrees of freedom for random distribution and is equivalent to a progressive extension of order. This is reflected by the frequencies of meta and para substitutions in the hexamer rings, which vary in a characteristical, continuous way with x, until the fully ordered distribution scheme of margarite (x=0.5) is reached. Partial long-range order for x

The Si, Al distribution in tetrahedral sheets of micas has been analysed by the use of Monte Carlo simulation and by the calculation of electrostatic energies. A new method for the calculation of electrostatic energies for short-range-ordered distributions has been developed. The results of the analysis demonstrate that the Si, Al distribution is mainly controlled by the electrostatic requirements of homogeneous dispersion of Al and local balance of inter-layer cations. Furthermore, electrostatic interactions between contiguous layers also constitute a significant factor controlling the tetrahedral cation distribution. Electrostatic energies of long-range-ordered models based in the para or in the meta disposition of Al are very similar, indicating that there is no preference for a particular long-range ordered distribution. This result justifies the distribution model found by NMR analysis, which is long-range-disordered, with the meta and para dispositions of Al equally favoured.

Three sepiolite clays studied showed evidence for the presence of structural hydroxyl groups in three to five different environments depending on the composition of the clay. A 3720 cm-l i.r. frequency is shown to be characteristic of SiOH at crystal edges which are very abundant in sepiolites. This band has not been seen by most workers because the Nujol, fluorolube or KBr used in sample preparation perturb it sufficiently to obscure it under other OH stretching bands. The 3680 cm-1 band is confirmed as being from the (Mg)aOH and evidence of a very small band near 3640 cm 1 is suggested to arise from limited trioctahedral substitution. The very crystalline Ampandrandava sepiolite shows only the above three bands. The intermediately crystalline Vallecas shows a 3620 cm-1 band in addition which is characteristic of dioctahedral systems and is due to either some vacancy sites or to the presence of attapulgite. This dioetahedral band is greater in the less crystalline Salinelles sepiolite; in addition, it has a smaller 3585 cm-1 band. Mg-Al-vacancy and Mg-Fe'"-vacancy are suggested as the source of the 3620 cm- 1 and 3585 cm- 1 bands.

The 27Al and 29Si magic-angle spinning nuclear magnetic resonance (MAS-NMR) study of the kaolinite-mullite transformation has shown the presence of Al in tetra- and pentacoordination in dehydroxylated kaolinite. The 29Si NMR signal analysis of samples heated above 400°C demonstrates that the tetrahedral sheet of kaolinite begins to break down near 600°C and continues to do so to 900°C. From the 27Al NMR signal evolution, it can be deduced that the exothermic peak at 980°C in DTA curves is associated with the modification of the coordination of Al, which changes from the tetra- or pentacoordination to the more stable octahedral coordination. Heating the sample at 880°C for 36 h produces the same transformation in the coordination of Al ions and the elimination of the exothermic peak at 980°C in the DTA diagram. After this transformation, all spectra show two tetrahedral lines characteristic of mullite, indicating that nuclei of mullite with low crystallinity are generated during the exothermic process which are not detected by XRD. At higher temperatures tetrahedral NMR peaks increase in intensity, yielding, at 1200°C, the 3:2 mullite NMR spectrum.

The analysis of 29Si MAR-NMR spectra of micas and vermiculite shows that the two main factors that govern the Si, Al distribution in the tetrahedral sheet of these minerals are: (i) Loewenstein's rule (avoidance of Al-O-Al linkages), and (ii) local balance of charges. In muscovite, phlogopite and vermiculite, Al is randomly distributed in hexagonal ring sites (meta and para dispositions equally favoured), but complying with the two above restrictions. In margarite Si and Al are observed to alternate strictly, in agreement with previous X-ray diffraction analysis.

29 Si NMR spectra of layer silicates with a wide range of tetrahedral composition (Si/Al ratios from 7.7 to 2.7) indicate that Si, Al distribution is mainly controlled by the electrostatic requirement of homogeneous dispersion of Al, confirming our earlier conclusions derived from the analysis of natural samples of micas with Si/Al ratios near to 3. This requirement includes, as a partial aspect, the Loewenstein's rule which forbids the presence of Al in neighbouring tetrahedra.

RésuméLes vermiculites Mg, Ca, Sr et Ba ont été étudiées par diffraction des rayons X et absorption infra-rouge.Pour les vermiculites monocouches, l'espacement interréticulaire est compris entre 12·2 et 11·45 Å.On distingue: (i) les vermiculites Ba; le cation, entouré de 5 à 6 molécules d'eau, est à environ 1Å du plan médian et il intéragit avec un hydroxyle structural du feuillet le plus proche, (ii) les vermiculites Mg, Ca et Sr; le cation, entrouré de 3 ou 4 molécules d'eau,est dans le plan médian ou dans son voisinage (0·3 Å), et il n'interagit pas avec les hydroxyles des feuillets.Pour les vermiculites anhydres, l'espacement interréticulaire est inférieur à 10 Å, le cation est dans le plan médian et il intéragit avec les hydroxyles de 2 feuillets opposés.A partir de ces résultats, complétés par les données de la bibliographie, des modéles sont proposés pour représenter l'organisation de l'espace interlamellaire.

Infrared spectroscopy affords a useful method for the determination of the orientation of molecules sorbed on layer silicates. The orientation of the molecules can be inferred from the observed dichroism of specific absorption bands. Examples of the analysis are illustrated in three complexes with pyridine. One flat and one vertical orientation are observed for the ionic form dependent on layer charge. A different vertical orientation is observed for the neutral molecule. The interpretation of the infrared absorption analysis is confirmed by X-ray diffraction.

The processes of dehydration and rehydration of montmorillonite and nontronite samples have been studied through infrared absorption spectra. The changes observed in the intensity of the bands during dehydration show the analogy between absorption at 915 cm-1 (montmorillonite) and at 820 cm-1 (nontronite), their origin being a deformation vibration of OH groups. During rehydration of the montmorillonite sample, the recovered OH groups occur in two different forms, in accordance with the results of differential thermal analysis.

Two octyl-ammonium vermiculite complexes with different 001 periodicities have been studied by i.r. spectroscopy. In each case i.r. spectroscopy affords information on the orientation of the-NH3 + groups and the strength of the hydrogen bond between these groups and the silicate oxygen surfaces. Also a perturbation of the vibration of the OH groups of the silicate has been observed that seems to be related to the distance from the center of the layer at which the-NH3 + groups are situated. The i.r. results are discussed in relation to the structural models deduced from X-ray analysis.

In recent years, the availability of high-field superconducting magnets complemented with mechanical spinning of the samples (magic-angle spinning technique) has resulted in a considerable improvement in resolution of NMR spectra and has widened the use of this technique in the structural analysis of solid samples. In particular, NMR spectroscopy can distinguish the different chemical environments of tetrahedrally coordinated silicon and also determine short-range order in the distribution of Si and Al in micas (Sanz et al., 1983) and zeolites (Fyfe et al., 1983; Klinowski et al., 1982).For aluminium (I = 5/2), the existence of strong quadrupolar interactions means that, in general, only the m½↔m−½ transition is observed. However, the signal is broadened by second-order quadrupolar effects, dipolar interactions and chemical shift anisotropies.

ORGANIC molecules sorbed on layer silicates generally adopt one single orientation. For those molecules for which the assignation of the absorption bands to the different vibrational modes has been well established, this association presents a favourable case for analysis by infra-red Spectroscopy. The orientation of the molecules can be inferred from the observed dichroism of specific absorption bands.

INFRA-RED spectroscopy has been found to be a useful method in establishing the orientation of OH bonds in layer silicates1. In micas and related forms of crystallization, the orientation of the OH depends on the occupancy of the octahedral positions. In trioctahedral compositions, the OH bonds are normal to the flakes and these groups are free of association in any supplemental bond (absorption band at 3,700 cm.-1). In dioctahedral minerals, the OH are inclined about 20° to the plane of the flakes and directed to the unoccupied octahedra; the absorption band is observed at 3,620 cm.-1, which indicates some degree of secondary association. © 1962 Nature Publishing Group.

The processes of dehydration and rehydration of montmorillonite and nontronite samples have been studied through infrared absorption spectra. The changes observed in the intensity of the bands during dehydration show the analogy between absorption at 915 cm–1 (montmorillonite) and at 820 cm–1 (nontronite), their origin being a deformation vibration of OH groups. During rehydration of the montmorillonite sample, the recovered OH groups occur in two different forms, in accordance with the results of differential thermal analysis.

Water vapour sorption isotherms on sodium and magnesium vermiculite of high charge density were measured at 25 and 50°C. Heats of immersion at various stages of hydration were measured at 25°C. According to X-ray observations during the sorption process, two discrete interlayer hydrates are obtained with one and two monolayers of water between the unit layers of the crystallites. The derived integral entropy of adsorption indicates a reduced freedom of motion of the interlayer water molecules compared with that for water molecules in the liquid state. Comparison of the apparent density of the hydrated clay with the calculated crystallographic density indicates that interlayer water is slightly more densily packed than liquid water. However, the bulk density of water in a sodium vermiculite suspension is normal for the water in excess of the two hydration layers.Nuclear pulse resonance results obtained on sodium vermiculite shows that water in the one-layer hydrate is organized and some hypotheses are presented regarding this organization. Water molecules in the two-layer complex show the same degree of orientation only below –65°C. Infra-red absorption spectra for hydrated flakes of sodium vermiculite were obtained as a function of angle between the (001) plane of the crystallites and the i.-r. beam. The results indicate orientation of water molecules in the one-layer hydrate at room temperature.

INFRA-RED spectroscopy has shown that only a small proportion of the external OH groups of kaolinite contribute to the bonding mechanism between layers and also that these interlayer hydrogen bonds are very weak (absorption bands above 3,600 cm−1) (ref. 1).

Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3\% and account for 20-30\% of all epilepsies. Despite their high heritability of 80\%, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out a two-stage genome-wide association study (GWAS) including 3020 patients with GGEs and 3954 controls of European ancestry. To dissect out syndrome-related variants, we also explored two distinct GGE subgroups comprising 1434 patients with genetic absence epilepsies (GAEs) and 1134 patients with juvenile myoclonic epilepsy (JME). Joint Stage-1 and 2 analyses revealed genome-wide significant associations for GGEs at 2p16.1 (rs13026414, P(meta) = 2.5 × 10(-9), OR[T] = 0.81) and 17q21.32 (rs72823592, P(meta) = 9.3 × 10(-9), OR[A] = 0.77). The search for syndrome-related susceptibility alleles identified significant associations for GAEs at 2q22.3 (rs10496964, P(meta) = 9.1 × 10(-9), OR[T] = 0.68) and at 1q43 for JME (rs12059546, P(meta) = 4.1 × 10(-8), OR[G] = 1.42). Suggestive evidence for an association with GGEs was found in the region 2q24.3 (rs11890028, P(meta) = 4.0 × 10(-6)) nearby the SCN1A gene, which is currently the gene with the largest number of known epilepsy-related mutations. The associated regions harbor high-ranking candidate genes: CHRM3 at 1q43, VRK2 at 2p16.1, ZEB2 at 2q22.3, SCN1A at 2q24.3 and PNPO at 17q21.32. Further replication efforts are necessary to elucidate whether these positional candidate genes contribute to the heritability of the common GGE syndromes.