Seizuredependent circuit rearrangements

Pilocarpine Epilepsy

The mesial temporal structures are interconnected by fibre systems that create the reverberating loop involving entorhinal cortex-dentate gyrus-CA3-CAl (subiculum)-entorhinal cortex. Dreier and Heinemann 52 have developed a technique for preparing in vitro slices including the full circuit and demonstrated that it is necessary and sufficient to sustain persistent epileptic activities. The most striking evidence of epileptogenic hippocampal plasticity was provided in 1969 by Goddard 53 , who...

Migraine

Migraine is surprisingly often mistaken for epilepsy, particularly when the headache is mild or absent 47 , Migrainous aura may have visual, sensory or motor features that may be suggestive of seizure activity, and alertness is sometimes impaired. Postictal headache is also common in epilepsy, and this can make the distinction more complicated than anticipated. Some unusual types of seizures, particularly those that originate in the occipital lobe, can be difficult to distinguish from migraines...

Sleep disorders

A review of the many abnormalities that arise from sleep is outside the scope of this brief review. However, sleep disorders such as periodic limb movements of sleep, REM sleep disorders, narcolepsy and cataplexy can be confused with seizures 60 . On the other hand some epilepsies arise exclusively from sleep and there is a propensity for partial seizures to occur in sleep or shortly after waking 61 . Benign rolandic epilepsy is an example of a seizure syndrome that is associated with sleep....

General approach to episodic disturbances

Since an enormous variety of conditions can cause episodes of transiently disturbed consciousness or function, the major component of clinical management consists of separating out the various causes. Determining the nature of events can be very challenging, particularly when the event has been unwitnessed or when the patient is an inadequate historian otherwise. Obtaining a clear account of the nature of the attack is the most important single component of the assessment, ascertaining...

Idiopathic localizationrelated epilepsies

Benign partial epilepsy of childhood The syndrome of benign partial epilepsy of childhood (BPEC) is also called benign rolandic epilepsy (BRE) and benign epilepsy of childhood with centrotemporal spikes (BECTS). The natural history is favourable for normal neurological and cognitive function plus eventual remission of epilepsy in more than 97 50 . It is characterized by the onset of usually infrequent partial seizures between ages 3 and 13 years. The temporal distribution of seizure favours...

References

1 Commission on Epidemiology and Prognosis, International League Against Epilepsy. Guidelines for epidemiologic studies on epilepsy. 2 Zielinski JJ. Epidemiology and Medicosocial Problems of Epilepsy in Warsaw. Final Report on Research Program no. 19-P-58325-F-01. Warsaw Psychoneurological Institute, 1974. 3 Granieri E, Rosati G, Tola Retal. A descriptive study of epilepsy in the district of Copporo, Italy, 1964-1978. Epilepsia 1983 24 502-14. 4 Maremmani C, Rossi G, Bonuccelli U, Murri L....

Eses Pseudo-lennox Landau-kleffner

On the anatomical, physiological and pathological investigation of epilepsies. West Riding Lunatic Asylum Med Reports 1873 3 315-39. 2 Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroen-cephalographic classification of epileptic seizures. Epilepsia 1981 22 489-501. 3 Gastaut H. Clinical and electroencephalographical classification of epileptic seizures. Epilepsia 1969 10 (Suppl.) 2-13. 4 Gastaut H....

Frings AGS Kindled rat

Fig. 8.1 Schematic diagram depicting the initial identification screen of the University of Utah Anticonvulsant Screening Project. Once accessioned, an investigational AED is screened for efficacy in both the MES and scPTZ tests. The activity of those compounds with demonstrated efficacy and minimal behavioural toxicity is quantitated at the time to peak anticonvulsant effect. Compounds found inactive in the MES and scPTZ tests are subsequently evaluated in the 6 Hz seizure test. The activity...

Epilepsy secondary to multiorgan hereditary disorders

Chromosome disorders include additions, deletions or rearrangement of chromosomal material. The most common chromosome disorder is Down's syndrome with an approximate incidence of 1 650 live births. Usually due to trisomy 21, triplication of 21q22.3 results in the typical phenotype. Epilepsy is present in up to 10 of cases and EEG abnormalities in more than 20 . Fragile X syndrome has an incidence of 1 1500 males while 1 1000 females are carriers. The X chromosome shows a fragile site atXq27.3....

Acute seizure models

The advantages of acute seizure model are reproducibility, and the ability to perform high throughput screening. The disadvantages are that the seizures do not mirror epilepsy i.e. spontaneous seizure occurrence and the seizures occur in 'normal', non-epileptic brains see above . There have been a variety of acute seizure models developed either using electrical stimulation or convulsant drugs. The two that have been most widely used are the MES and PTZ models. Other convulsants include a...

Incidence and prevalence of idiopathic cryptogenic and symptomatic epilepsy

The study of the incidence, prevalence and characteristics of epilepsy in well-defined populations has several advantages, including the calculation of the fraction of epilepsy attributable to known aetiological factors remote symptomatic epilepsies , the frequency of well-established risk factors for unprovoked seizures e.g. head trauma, CNS infection, degenerative disorders, stroke, febrile seizures, cerebral palsy and mental retardation and the fraction of known aetiology attributable to...

Animal models of drug resistance in epilepsy

As for refractory epilepsy in humans, AED resistance in animal models has received little attention. Mice bred for their proneness to ethanol withdrawal convulsions are more resistant to various AEDs including phenytoin 37 , whilst the genetically-susceptible El mouse has delayed phenytoin-induced upregulation of voltage-dependent sodium channels compared to normal mice 38 . These aspects have received little further attention. The model best studied is the amygdala-kindled phenytoin-resistant...

Contents

31 Short-Acting and Other Benzodiazepines 374 L.J. GreenfieldJrandH.C. Rosenberg 32 Ethosuximide 391 T.A. Glauser 33 Felbamate 403 I.E. Leppik 34 Fosphenytoin 410 R.E. Ramsay and F. Pryor 35 Gabapentin 418 T.R. Browne 37 Levetiracetam 443 A. Sadek and J. A. French 38 Oxcarbazepine 451 E. Faught 39 Ph nobarbital, Primidone and Other Barbiturates 461 R. Michelucci and C.A. Tassinari 40 Phenytoin 475 M.J. Eadie 41 Piracetam 489 S.D. Shorvon 42 Pregabalin 496 E. Ben-MenachetnandA.R. Kugler 43...

General epidemiology

The size of the epilepsy population, prevalence In order to compare the prevalence of epilepsy in different groups, the definition of epilepsy should be the same across studies. The definition of epilepsy recommended by international guidelines for epidemiological studies of epilepsy states that seizures should be recurrent i.e. at least two seizures should have occurred and unprovoked by any immediate identified cause 1 . To be able to generalize results, ascertainment of cases within the...

H

Mes Merritt And Putnam Boston

Fig. 1 Comparison of the structure of early barbiturate and hydantoin drugs showing their similarity. The barbiturates, hydantoins, oxalolidine diones, succinimides and phenacemide are all based on the ureide moiety with different side-chains Rl,R2-C-CO-NH-CO-R3 This was well recognized by medicinal chemists at the time who deliberately synthesized ureide derivatives in the hope of finding improved clinical action. Fig. 1 Comparison of the structure of early barbiturate and hydantoin drugs...

MES test

One of the seminal discoveries of the last 150 years of epilepsy research was the discovery that electrical stimulation in animals subsequently generated seizures. The MES model is one of the most commonly used models of this type. The MES test involves either bilateral corneal or transauricular electrical stimulation and subsequently induces tonic hind limb extension and flexion followed by clonus. Traditionally, drugs that exhibit an affinity in blocking seizures generated by this model find...

The ketogenic diet

Of all the ancillary therapies being championed in the 1930s, the ketogenic diet requires special mention, as it remains of marginal interest right up to the present time see Chapter 21 . Lennox 1 records his version of how the ketogenic diet was introduced. In the 1920s, a New York corporate lawyer consulted an osteopathic physician concerning his son who had severe epilepsy. A water diet was recommended, which consisted of starvation of 3 or 4 weeks. Dramatically, the seizures were relieved....

The treatment of epilepsy between 1938 and 1945

Lennox's literature reviews and the summaries of epilepsy practice in the different countries notably in the USA in these years in Epilepsia provide an excellent vantage point to view the progress of epilepsy therapy in the years 1938-45. The first literature review was published in 1938 actually a review of the year 1936 . Thirteen articles on treatment were reviewed, and these were concerned with bromides, phenobarbital, prominal, antirabies vaccine, ergotamine tartrate, subarachnoid air...

Glutamate and glutamate receptors

Glutamate is a non-essential amino acid that does not cross the blood-brain barrier, but is readily synthesized by various biochemical pathways from different precursors including a-ketoglutarate an intermediate of the Krebs' cycle , glutamine, ornithine and proline 133 , GAB A transaminase contributes to the synthesis of glutamate Fig. 9.5 . Thus vigabatrin, which inhibits GABA transaminase, as well as inhibiting the breakdown of GABA may also decrease the synthesis of glutamate 134 ....

Cgp

Fig. 9.7 Activation of GABABRs by release of GABA from a single interneurone. al Dual recording from a connected interneurone pyramidal cell in pyr pair. Three action potentials triggered in the interneurone elicit three inhibitory postsynaptic currents in the pyramidal cell. A train of action potentials 100 Hz from the interneurone elicits an outward current in the pyramidal cell. Both types of responses are completely blocked by the GABAaR antagonist bicuculline. Addition of the GABABR...

What is the future of AED discovery and development

Since its inception in 1975, the Anticonvulsant Screening Project, Utah, has screened over 24 000 investigational AEDs. In addition to the compounds that have been successfully developed, a number of additional compounds are in various stages of clinical development. Each of these drugs has brought about substantial benefit to the patient population in the form of increased seizure control, increased tolerability and better safety and pharmacokinetic profiles. Unfortunately for 25-40 of...

Diphenylhydantoin phenytoin

The introduction of phenytoin was of course a major step in the history of epilepsy, neurology and clinical pharmacology. It transformed the treatment of epilepsy, it changed the conceptual basis of epilepsy practice, the approach to drug discovery, the role of the pharmaceutical company in epilepsy, the organization of epilepsy care and indeed the whole international epilepsy movement. I doubt whether any other single treatment, with the possible exception of ph nobarbital, has had such an...

Thalamocortical circuitry

It has long been known that thalamocortical circuits play a role in the generation of spikes and waves 72,73 , The results obtained in GAERS presenting with absences associated with 7 Hz spike-wave complexes have shed light on the rhythmogenic thalamic mechanisms responsible for the paroxysmal discharges 31-33,74 , A key role is played by the reticular thalamic nucleus, a laminar structure enfolding the anteroventral and lateral aspects of the dorsal thalamus that is entirely made up of...

Movement disorders

A number of movement disorders can imitate epilepsy. Paroxysmal choreoathetosis or dystonia, both kinesogenic and non-kinesogenic forms 72 , are movement abnormalities with striking posturing or chorea that are precipitated by sudden movement, surprise or startle, stress or rapid movement. Some forms are aggravated by alcohol, caffeine and fatigue. Whereas these may be unilateral and consciousness is preserved during the attacks, the episodes may be mistaken for focal motor seizures. Thus the...

Info

Note Epilepsia has had a confusing system of numbering its issues caused by the interruption of publication on three occasions creating 4 'series' and changes in editorial policy. The original conception was of a single volume annually, each comprising four quarterly issues. Actually in 7 years of its existence, only five volumes were produced. When series II was initiated in 1937, it was planned to have one volume covering a 4-year period, with one issue a year. This scheme was followed...

Clinical implications

Although based on incomplete evidence, the following strategies for the prevention of SUDEP cases would be reasonable Seizure prevention, particularly generalized tonic-clonic seizures this should be achieved through active medical and surgical treatment, avoiding seizure pr cipitants and through patient and physician education. Avoiding abrupt medication changes. Ensuring prompt response to seizures with advice on first aid and positioning stimulating the patient if there is any respiratory...

Membrane ion channels

Epilepsy Diary

The excitability of nerve cells depends on the movement of ions through specific voltage-dependent or receptor-activated membrane channels. The kinetics of transmembrane ion currents have been extensively investigated by means of various types of voltage clamp recordings. The effects of ion currents on cell membrane potential can be detected by means of current clamp recordings. Ion channels are heterooligomeric membrane proteins typically consisting of 2-6 subunits, including transmembrane...

GABA and GABA receptors

Gaba Shunt

GABA is the major inhibitory neurotransmitter in the brain. It is formed and degraded in the GABA shunt Fig. 9.5 . Glutamic acid decarboxylase GAD converts glutamate to GABA. Promotion of GABA synthesis has been proposed to contribute to the action of some antiepileptic drugs including valproate 56 . GABA is degraded by GABA transaminase to succinic semialdehyde a-ketoglutarate accepts the amino group in this reaction to become glutamate Fig. 9.5 . GABA is transported into vesicles by the...

Prenatal and perinatal risk factors

Pre- and perinatal risk factors include toxaemia and eclampsia during pregnancy, low birth weight, asphyxia and other neonatal abnormalities, and other less defined conditions 38 , Although the role of these factors in the aetiology of epilepsy seems established, most of the earlier studies yielded relative risks RRs or ORs below 10, which indicate, at best, a moderate association between pre- and perinatal factors and subsequent epilepsy Table 4.7 . Even in a more recent population-based study...

Nmdar

Atx Patch Clamp

Fig. 6.2 Ligand-gated a and voltage-gated b channel involvement in paroxysmal depolarization shift PDS generation. First row schematic representation of GABAergic a, andglutamatergic a2 synapses and of Na , Ca2 and K channels bj . Flat and round vesicles are respectively recognizable in GABA and glutamate containing presynaptic endings. Ionotropic receptors R are depicted on the postsynaptic membrane GABAC-R not shown . The inferior part of the figure shows a schematic representation of the...

Prognosis in largely untreated populations

The natural history of epilepsy can be derived from untreated or largely untreated epilepsy populations. In less developed countries the vast majority of patients with epilepsy do not receive pharmacological treatment 158 for their epilepsy and would thus be suitable for the study of natural prognosis. In practice, however, once a patient with epilepsy is identified in a study it would be unethical to withhold AED treatment. A prospective study of the natural history is no longer possible once...

CNS infections

CNS infections are a major risk factor for epilepsy. Seizures may be the presenting or the only symptom, or may be one component of a diffuse brain involvement. Using the incidence of epilepsy expected in the general population for reference, the risk of epilepsy among individuals with encephalitis or meningitis is increased almost seven-fold 43 . This increased risk is highest during the first 5 years after infection and tends to decrease thereafter, but it remains elevated up to 15 years. The...

The MES and scPTZ tests

The MES and scPTZ seizure models continue to represent the two most widely used animal seizure models employed in the search for new AEDs 5,8,9 and presently remain as the primary screens of the Anticonvulsant Screening Project Fig. 8.1 . As mentioned above, Merritt and Putnam successfully employed the MES test in a systematic screening programme to identify phenytoin 6 . This observation when coupled with the subsequent success of phenytoin in the clinical management of generalized...

Genetic models

Until recently, genetic models of epileptic disorders had to rely on animals with an inherent susceptibility to display seizure activity. However, recent advances have made it possible to study the effects of genetic modification and how these subtle changes lead to epilep-togenesis at the cellular level. Moreover, a greater understanding of the anatomical and physiological adaptations that occur following the expression of the 'epileptic gene' may pave the way for improved pharmacotherapy of...

Contributors

Professor of Neurology, School of Medicine, Room 794-M, University of California, San Francisco, CA 94143-0114, USA Associate Professor of Neurology, Medical College of Wisconsin and Director, Comprehensive Epilepsy Program and EEG Laboratory, Froedtert Hospital, 9200 West Wisconsin Avenue, Milwaukee, WI53226, USA President of the International League Against Epilepsy, Professor of Medicine and Director of the Department of Clinical Neurosciences. Istituto Nazionale Neurologico C Besta, Via...

Sodium channels

Sodium channels provide the major target for a number of antiepileptic drugs Table 9.1 . Voltage-gated sodium channels are responsible for the rising phase of the action potential in excitable cells and membranes, and are thus critical for action potential generation and propagation 1 . The sodium channel exists in three principle conformational states a at hyperpolarized potentials the channel is in the resting closed state b with depolarization the channels convert to an open state that...