Seizure severity scales have recently been identified as an important additional outcome measure in trials of new antiepileptic drugs (AEDs). The National Hospital Seizure Severity Scale (NHS3) is presented as a refined version of the Chalfont Seizure Severity Scale. The principal advantages of the new version are that it is quicker and simpler to apply, the limits of reliability are now clearly defined, and construct validity for the scale is available. The scale is administered by a health professional during an interview with a patient and a witness to the seizures. It contains seven seizure-related factors and generates a score from 1 to 27. An intraclass correlation coefficient of 0.90 was obtained during interobserver and test-retest reliability assessment, suggesting that the scale is sufficiently reliable for group studies. Scores for an individual patient should be interpreted with caution in light of the limits of agreement obtained. Validation experiments indicate that NHS3 measures seizure severity in a manner compatible with the subjective impression of people with epilepsy. We suggest that the NHS3 is a valid, easily applicable measure of seizure severity that is acceptably reliable for use in trials of novel AEDs.

It is now widely acknowledged that the impact of epilepsy on the individual extends beyond the occurrence of seizures, and that there is a need for outcome measures sensitive to these consequences. Until now these instruments have largely been developed within a 'quality of life' framework. The technical and conceptual difficulties that arise with measuring quality of life have led us to develop a more focused measurement model, the 'Subjective Handicap of Epilepsy' (SHE) scale, based on the World Health Organization's concept of handicap. The scale contains 32 items in six subscales: 'Work and activities' (eight items), 'Social and personal' (four items), 'Self-perception' (five items), 'Physical' (four items), 'Life-satisfaction' (four items) and a 'Change' scale (seven items); and it takes on average < 10 min to complete. The scale's test-retest reliability was found to be satisfactory (intra-class correlation coefficient was 0.8-0.9 in 110 subjects). The test-retest interval (24 h to 8 weeks) had no influence on the reliability. The reliability was also not affected by minor recent fluctuations in seizure frequency. The internal consistency of the scales was 0.8-0.9 (Cronbach's alpha). The construct validity of the scale was examined in a sample of 287 clinic attendees at a university neurology clinic in the UK. The scales were highly sensitive to the handicapping effects of increasing seizure frequency, employment status, the impact of epilepsy on career choice and the subject's own opinion as to the major determinant of their quality of life. The scales were also sensitive, retrospectively, to the benefits of successful epilepsy surgery in a cohort of 105 patients. Scales focusing specifically on handicap were more sensitive to group differences in seizure frequency in the clinic population, and to outcome after epilepsy surgery, than the 'Life-satisfaction' scale and the Epilepsy Surgery Inventory 55 (ESI-55) scales. This supports the contention that measuring 'subjective handicap' may be a more sensitive, and more useful, approach to assessing the impact of interventions on the long-term consequences of epilepsy than current methods.

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Summary:Recent studies indicate that the overall mortality rate for persons with epilepsy is elevated two-or threefold compared with the general population. The standardized mortality ratio (SMR) is greatest in the first few years after diagnosis and in symptomatic epilepsies. Idiopathic epilepsies also have a small increase in SMR. The sudden unexpected death rate in those with epilepsy (SUDEP) depends on the population examined. In the general population of persons with epilepsy,

The endogenous cannabinoid system regulates neuronal excitability. The effects of inhibiting fatty acid amide hydrolase (FAAH), the enzyme responsible for metabolism of the endocannabinoid anandamide, on kainic acid (KA)-induced neuronal activity were investigated in the rat in vivo, using the selective FAAH inhibitor URB597. Hippocampal neuronal ensemble unit activity was recorded in isoflurane-anesthetized rats using 16-wire microelectrode arrays. Separate groups of rats were administered with single doses of KA alone, KA and URB597 (0.3 or 1 mg kg 21 , i.p.), or URB597 (1 mg kg 21 ) alone. The role of the cannabinoid CB1 receptor in mediating the effects of URB597 was explored using the CB1 selective antagonists AM251, either alone or prior to KA and URB597 (1 mg kg 21 ) administration, and SR141716A, administered prior to KA and URB597 (1 mg kg 21 ). Neuronal firing and burst firing rates were examined in animals with confirmed dorsal hippocampal placements. KA induced an increase in both firing and burst firing rates, effects which were attenuated by URB597 in a dose-related manner. Pretreatment with AM251 or SR141716A partly attenuated the URB597-mediated effects on firing and burst firing rate. Rats treated with AM251 or URB597 alone did not exhibit any significant change in either firing or burst firing rates compared with basal activity. These results suggest that the inhibition of endocannabinoid metabolism can suppress hyperexcitability in the rat hippocampus, partly via a CB1 receptormediated mechanism. Synapse 62: 746-755, 2008. V

Antihistamines that bind to the histamine 1 receptor (H1) serve as important therapeutic agents to counter the effects of histamine in the skin. Two generations of antihistamines exist; however, second-generation agents are more advantageous because they cause less sedation, have a longer half life and are more selective for the H1 receptor. While H1 antihistamines have proven to be effective at reversing the pruritus and cutaneous lesions of chronic urticaria, their ability to treat pruritus associated with other cutaneous and systemic diseases is unproven.

Remission rates for JAE and JME was lower than expected. Higher proportions of seizure free patients underwent physician-supervised withdrawal than anticipated. Relapse rates off AEDs were similar for JAE and JME, and at least twice as high as for those remaining on AEDs, and a further remission was not invariable on restarting AEDs. Our experience, comparing relapse in those withdrawing to those staying on AEDs will help in discussions with patients keen to try AED withdrawal.

SUMMARY -We report the case of a patient with trisomy 21 (T21) with late onset epilepsy. The electroclinical features were of myoclonic jerks on awakening and generalised tonic clonic seizures, with generalised spike and wave on EEG, and a progressive dementia. As familial Alzheimer's dementia and progressive myoclonic epilepsy (Unverricht-Lundborg type) are both linked to the chromosome 21, this case may represent a distinct progressive myoclonic epilepsy related to T21.KEY WORDS: myoclonic epilepsy, Down's syndrome, trisomy 21. Epilepsia mioclônica de início tardio na trissomia 21RESUMO -Pacientes com trissomia do cromossoma 21 (T21), com o passar dos anos, são propensos a desenvolver crises epilépticas parciais concomitantes ao aparecimento de degeneração cerebral do tipo Alzheimer. Pacientes com T21 e demência parecem ter risco maior de apresentarem crises epilépticas que outros pacientes com degeneração cerebral do tipo Alzheimer. O caso relatado é de um paciente com T21 com epilepsia de início tardio. A história clínica consiste de crises mioclônicas ao despertar, ocasionais crises generalizadas tônico-clônicas, demência e ponta onda generalisada no EEG. Demência do tipo Alzheimer familial é ligada ao cromossoma 21, bem como epilepsia mioclônica progressiva (tipo Unverricht-Lundborg). Isto sugere que este caso possa representar um tipo distinto de epilepsia mioclônica progressiva, ligado ao cromossoma 21. PALAVRAS -CHAVE: epilepsia mioclônica, síndrome de Down, trissomia do cromossoma 21.Patients with trisomy 21 (T21) have a higher prevalence of epilepsy than the general population 111215 . Amongst T21 patients, the onset of epilepsy has a bimodal distribution, being more common in early childhood and after the third decade 1215 . A dementia of the Alzheimer type is frequent in T21, specially after the fourth decade of life 916 . This has become more apparent as the life expectancy of T21 has increased over recent years 1 . Partial seizures are the commonest type of seizures described in late onset epilepsy in patients with T21 4 -111215 . However, Genton and Paglia 5 -5 have recently reported three patients with T21 with late onset epilepsy, whose clinical features included myoclonic jerks on awakening and tonic clonic seizures. We report here a similar case.