Samden D. Lhatoo

Topiramate and Psychiatric Adverse Events in Patients with Epilepsy

Summary: u2002Purpose: The aim of this study was to determine the prevalence of psychiatric adverse events (PAEs) in patients with epilepsy treated with topiramate (TPM). Classification, relation to TPM dosing, and outcome were evaluated to identify a patient profile at risk of developing PAEs.

Long-term retention rates of lamotrigine, gabapentin, and topiramate in chronic epilepsy

PURPOSEnWe sought to determine the long-term retention rates of lamotrigine (LTG), gabapentin (GBP), and topiramate (TPM) therapy for patients at a tertiary referral clinic for chronic, refractory epilepsy.nnnMETHODSnWe analyzed 424 consecutive patients with chronic, refractory partial and/or generalized epilepsy who were started on LTG, 158 patients who were started on GBP, and 393 patients who were started on TPM. The percentages of patients who continued therapy with LTG, GBP, and TPM were estimated with the use of Kaplan-Meier survival analysis. Factors that influence retention were analyzed with the use of Cox regression analysis.nnnRESULTSnKaplan-Meier survival analysis showed that at 3 years, 30% continued therapy on TPM compared with 29% on LTG and fewer than 10% on GBP. Adverse events resulted in therapy withdrawal in 40% of patients on TPM compared with GBP (37%) and LTG (22%). Perceived lack of efficacy led to treatment withdrawal in 39% of patients on GBP compared with 34% on LTG and 19% on TPM. Cox regression estimated that a fourth or fewer of patients with chronic partial epilepsy are likely to continue therapy with a new antiepileptic drug beyond 5 years.nnnCONCLUSIONSnThe impact of these new antiepileptic drugs on the long-term course of chronic partial epilepsy is likely to be small, as approximately three of four patients will discontinue therapy. More patients appear to continue on TPM compared with LTG or GBP, with a possible reason being better perceived efficacy of TPM, despite having the highest incidence of adverse events.

The epidemiology of epilepsy and learning disability

Epilepsy, the most prevalent serious neurological disorder, afflicts 0.5% of the general population (1). The prevalence of learning disabilities (LDs) in the general population is approximately similar (2). Both groups of conditions share a common heritage of heterogeneity, high prevalence figures, a dearth of care expertise outside major centres or institutions, and an unfortunate degree of stigmatization. Up to a fourth of patients with epilepsy are said to have LDs, and conversely, up to half of all patients with LDs are said to have seizure disorders, thus rendering this particular combination an especially common one. The paucity of authoritative studies on prognosis, mortality, and treatment of this special group belies this, however, and is all the more surprising. This encourages a substantial lacune in current knowledge of the epilepsies, and these deficiencies must be addressed appropriately.

CNS Adverse Events Associated with Antiepileptic Drugs

AbstractA variety of newer antiepileptic drugs (AEDs) are now available for treating patients with epilepsy in addition to the ‘conventional’ drugs that have been available throughout a large part of the last century. Since these drugs act to suppress the pathological neuronal hyperexcitability that constitutes the final substrate in many seizure disorders, it is not surprising that they are prone to causing adverse reactions that affect the CNS.Information on adverse effects of the older AEDs has been mainly observational. Equally, whilst the newer drugs have been more systematically studied, their long-term adverse effects are not clearly known. This is illustrated by the relatively late emergence of the knowledge of visual field constriction in the case of vigabatrin, which only became known after several hundred thousand patient-years of use. However, older drugs continue to be studied and there has been more recent comment on the possible effect of valproate (valproic acid) on cognition following exposure to this drug in utero.n With most AEDs, there are mainly dose-related adverse effects that could be considered generic, such as sedation, drowsiness, incoordination, nausea and fatigue. Careful dose titration with small initial doses can reduce the likelihood of these adverse effects occurring. Adverse effects such as paraesthesiae are more commonly reported with drugs such as topiramate and zonisamide that have carbonic anhydrase activity. Weight loss and anorexia can also be peculiar to these drugs. Neuropsychiatric adverse effects are reported with a variety of AEDs and may not be dose related. Some drugs, such as carbamazepine when used to treat primary generalized epilepsy, can exacerbate certain seizure types. Rare adverse effects such as hyperammonaemia with valproate are drug specific. There are relatively very few head-to-head comparisons of AEDs and limited information is available in this regard.In this review, we discuss the available literature and provide a comprehensive summary of adverse drug reactions of AEDs affecting the CNS.

A prospective study of the requirement for and the provision of epilepsy surgery in the United Kingdom.

Summary: u2002Purpose: Of the 30,000 persons in whom epilepsy develops annually in the United Kingdom, in ∼6000 (20%), intractability develops. Some of these patients will be appropriate for epilepsy surgery. We aimed to estimate the number of patients who should be considered surgical candidates, by extrapolation from a population‐based study of prognosis and the number who are receiving epilepsy surgery, by a survey of U.K. neurosurgeons.

The dynamics of drug treatment in epilepsy: an observational study in an unselected population based cohort with newly diagnosed epilepsy followed up prospectively over 11–14 years

OBJECTIVES To study prospectively long term dynamics and patterns of treatment in a population based cohort of patients with newly diagnosed epilepsy. METHODS 564 patients with definite epilepsy entered the UK National General Practice Study of Epilepsy (NGPSE), between 1984 and 1987, and were prospectively followed up for between 11–14 years. RESULTS Treatment was started in 433 (77%) patients. Only 15% of single seizure patients had medication prescribed initially, although due to high seizure recurrence, more than 70% ultimately received antiepileptic medication. 209/564 patients (37%) were on drug therapy for epilepsy at the time of last follow up. 168/564 patients (30%) have stayed continuously on medication and another 41/564 patients (7%) restarted drug therapy because of seizure recurrence, having withdrawn medication. 98/209 (47%) of those on treatment are known to be in 5 year terminal remission. Phenytoin (29%) and carbamazepine (27%) were the most commonly preferred first line drugs followed by valproate (15%). Less than half of treated patients with partial seizures received carbamazepine as a first line drug and less than a third with generalised seizures were prescribed valproate as first choice drug. Nine out of 31 (29%) patients with one or more seizures a week at last follow up had never tried a second drug and only seven (23%) had tried four or more drugs. 11% of all treatment changes involved a new antiepileptic drug. Treatment changes were associated with low terminal remission rates. CONCLUSIONS Out of 30u2009000 patients with newly diagnosed epilepsy every year in the United Kingdom, about 6000 have inadequate seizure control in the long term. About a third of the patients in this group have one or more seizures every month. Only two thirds of these patients with frequent seizures are likely to switch medication to try and achieve better seizure control. There is probably still considerable room for improvement in prescribing practice in the United Kingdom.

The surgical treatment of status epilepticus

While the role of surgery in the management of refractory focal epilepsy is established, it is much less frequently used in the treatment of status epilepticus (SE). With the exception of hemispherectomy in the epilepsia partialis continua of Rasmussen’s encephalitis, current literature on the subject comprises a handful of small case series and anecdotal reports of disparate surgical procedures (Table 1), almost exclusively where SE is deemed refractory (RSE). In the situation of RSE caused by radiologically and/or electrophysiologically definable focal brain pathology, the role of surgical resection would appear an intuitive and logical one, although it does not often translate into clinical practice. Given its potential as a life-saving intervention, there is requirement for a better definition and understanding of the place of surgery in the modern management of SE.

Epilepsy surgery for refractory epilepsy due to encephalocele: a case report and review of the literature

The management of medically intractable epilepsy is frequently assisted by the identification of structural abnormalities made possible by modern imaging techniques. The association between meningoencephaloceles and epileptic seizures is well reported in the literature. We report a patient with refractory right frontal lobe epilepsy caused by a right nasal meningoencephalocele who was rendered seizure free by endoscopic nasal excision and skull base repair, obviating the need for resective epilepsy surgery. Epilepsy patterns associated with encephalocele and their management are reviewed.

Familial Idiopathic Brain Calcification – A New and Familial α-Synucleinopathy?

Familial idiopathic brain calcification (FIBC) is a rare disorder characterised by autosomal dominant transmission, adult onset cerebellar and/or extrapyramidal features and idiopathic calcification of the brain. We present a family with FIBC where pathological studies showed that the proband had α-synuclein-immunopositive glial and neuronal cytoplasmic inclusions in oligodendrocytes in the putamen, midbrain and pons. This may represent a new and familial α-synuclein disorder causing a predominantly extrapyramidal picture similar to multisystem atrophy.

Horner's syndrome postpartum

Sir, Merrison and and Samden describe an interesting and rare case of postpartum Horner’s syndrome in a young lady presenting two weeks after delivery. The authors describe prolonged labour with forceps assisted delivery of a healthy 10 lb baby. The authors have postulated straining during labour with unusual neck movements and high spinal anaesthesia as possible mechanisms for this rare phenomenon that possibly resulted in dissection and acute thrombosis of the extracranial internal carotid artery. We were surprised to read the mode of assisted delivery and were at loss to know what could possibly be the indication for ‘high’ forceps application, which is rarely practised in modern obstetrics. Horner’s syndrome is now a well-recognised complication of spinal anaesthesia or analgesia during labour. However, it is usually an immediate occurrence. Two-week latency in this case makes it difficult to associate the spinal anaesthesia with such a delayed onset of Horner’s syndrome, especially in the absence of any associated delayed neurological deficits. The authors have also discussed possibility of neck movements during the delivery as another possible mechanism of the Horner’s. Considering that a significant proportion of women do assume unusual neck posture at some stage during the second stage of labour, one would have expected Horner’s syndrome to occur much more commonly if it was mainly related to intrapartum neck movements. Even in patients with severe cervical spine injuries, Horner’s syndrome is rare in the absence of spinal cord involvement. From the history provided, the patient in the case described was young and was not susceptible to carotid dissection in any way and should not have normally developed any neurological deficit with voluntary neck movements during labour. Although both the mechanisms postulated by the authors are valid, they do not convincingly establish a cause and effect relationship in this case. On the contrary, it is possible that she may have developed thrombosis of her internal carotid artery spontaneously. Although intracranial venous system is more prone to thrombosis in puerperium—mainly due to its slow blood flow and low pressure, the arterial system is by no means completely exempt from such a phenomenon. Difficult delivery, prolonged labour with possible dehydration, spinal anaesthesia with further hypotension and slowing of the blood flow in combination with the natural hypercoagulability of the blood normally seen in puerperium may have resulted in spontaneous internal carotid thrombosis, obliteration of vasa nervosa and subsequent Horner’s syndrome. Complete resolution of symptoms with anticoagulation within three months supports this theory that there was no anatomical disruption of the sympathetic fibres, which would have been the case if it was due to trauma caused by neck movements.