References

Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota 1935-1984. Epilepsia 1993 34 453-468. 2. Bladin CF, Alexandrov AV, Bellavance A et al. Seizures after stroke a prospective multicenter study. Arch Neurol 2000 57 1617-1622. 3. Vespa PM, O'Phelan K, Shah M et al. Acute seizures after intracerebral hemorrhage a factor in progressive midline shift and outcome. Neurology 2003 60 1441-1446. 4. Arboix A, Garcia-Eroles L, Massons JB et al....

Infantile sPAsMs AND west sYNDRoME

Natural or synthetic adrenocorticotropic hormone (ACTH), glucocorticosteroids and vigabatrin (VGB) are the main pharmacological agents currently suggested for the treatment of infantile spasms (IS). In addition, conventional and newer anti-epileptic drugs, as well as vitamin B6, are used. There is no agreement which agent should be commenced first line. Protocols differ in dosing regimes as well as duration of treatment courses, depending on geographical area and availability of these agents....

Pharmacomechanistic Approach to AED Combinations

Combining drugs with different mechanisms of action is a common strategy in the treatment of many medical disorders. Polytherapy is also used routinely in some neurological conditions, even at treatment initiation. Thus, in patients with Parkinson's disease, levodopa is combined with a dopa decarboxylase or catechol-o-methyltransferase inhibitor to reduce its systemic breakdown. Likewise, it is plausible to obtain a synergistic (supra-additive) effect in the drug treatment of epilepsy by...

Perimenopause And Menopause

Women with epilepsy report increased seizure frequency with perimenopause 91 . Thirty-nine women with epilepsy in perimenopause, as manifested by irregular menses and hot flushes, were surveyed regarding change in seizure frequency as they became perimenopausal. Most of the women (63 ) reported an increase in seizure frequency as they became perimenopausal, although their medication had not been changed. Women who had a history of a catamenial seizure exacerbation, specifically pre-menstrual...

Treatment oF BIPoLAR DisoRDERs IN PwE

Bipolar disorder is an episodic lifelong disease which may begin with a manic, hypomanic or depressive episode. If the bipolar disorder goes untreated, patients may experience 10 or more episodes in the course of their lifetime. While 4-5 years may elapse between the first two episodes, intervals shorten between subsequent episodes. Bipolar patients constitute about 20 of patients with an affective disorder in non-epilepsy patients the actual prevalence of bipolar disease in PWE remains...

The Ketogenic Diet

After a decline in use, the ketogenic diet has made a strong comeback since the early 1990s. It is now considered to be one of the standard medical therapies in children with epilepsy. It is not considered to be a treatment of first choice for any type of seizure or epilepsy syndrome, except for a few specific conditions that are particularly or exclusively responsive to the ketogenic diet, such as glucose transporter type I defect, pyruvate dehydrogenase complex deficiency, ketotic...

Step Three Mandatory Investigations

The following are considered mandatory investigations at most major epilepsy centres, and each will be discussed separately. High-resolution magnetic resonance imaging (MRI) can be very helpful in detecting epileptogenic structural lesions. According to the American Academy of Neurology guidelines for evaluation of a first unprovoked seizure, brain imaging with computerized tomography (CT) or MRI is recommended and was given a Level B classification 17 . Of course, the EZ might extend beyond...

F

Facial weakness, as side-effect of vagus nerve febrile status epilepticus, risk of subsequent epilepsy 256 feeding difficulties, association with intellectual disability 307 felbamate 9, 15, 96, 148 drug interactions 144, 240, 243, 244 with oral contraceptives 154 initiation of therapy 16 mechanism of action 141 side-effects 179 use in elderly patients 181 use in liver disease 234 use in patients with intellectual disability 310 use in renal disease 232 fertility 130, 162-3 first seizures 87...

NEuRoprotection In StatuS EpilepticuS

As discussed, prolonged seizures may result in neuronal death, which in turn may lead to cognitive decline and epilepsy. As the mechanisms underlying neuronal death in SE become better understood, research has focused on methods of preventing the pathophysiological changes that result in neuronal damage. Thus, most potential neuroprotective agents have targeted excitotoxic pathways, including blockade of glutaminergic NMDA receptors and calcium channels or, alternatively, apoptotic pathways....

Pharmacokinetic Interactions Between Aeds And Antidepressants Impact of AEDs on Antidepressants

Traditional AEDs such as phenytoin, carbamazepine and phenobarbital are potent inducers of the cytochrome P450 CYP enzyme system. Oxcarbazepine and topiramate are much less potent inducers of CYP 3A4. AEDs including gabapentin, pregabalin, levetiracetam, tiagabine and lamotrigine do not appear to interfere with CYP activity. The majority of anti-depressant drugs are substrates for one or more or the CYP isozymes 20 . Therefore, co-medication with an enzyme-inducing AED would be expected to...

Ilae Guidelines Newly Diagnosed Epilepsy

ILAE guidelines state that CBZ, LTG, OXC, PH, PHT, TPM and VPA are possibly efficacious effective as initial monotherapy for adults with GTC seizures and may be considered for initial therapy in selected situations recommendation level C . In children with GTC seizures, CBZ, PB, PHT, TPM, and VPA are possibly efficacious effective and may be considered for initial monotherapy. No clear first choice exists individualized prescription is encouraged. However, the guidelines state that CBZ, OXC and...

Alternate Psychosis Or Forced Normalization

The concept of alternate psychosis was developed from observations in 1953 by Landoldt, of an inverse relationship between seizure control and psychotic symptom occurrence, in which he observed a 'normalization' of EEG recordings with the appearance of psychiatric symptoms and coined the term 'forced normalization' 56 . This antagonism between psychosis and epilepsy has been considered by some as the explanation for the therapeutic effect of ECT of psychotic disorders. Forced normalization has...

Treatment Of Ige With Gtc Seizures Only

The syndrome of primary GTC seizures presents the clinician with nosologic, diagnostic and treatment difficulties. Some patients with IGE appear to have GTC seizures alone and the 1989 ILAE epilepsy classification individualized epilepsy with grand mal seizures on awakening and epilepsies with specific modes of precipitation 38 . The evolving classification of IGE uses more inclusive terms such as IGE with GTC seizures only 39 and IGE with pure grand mal seizures 40 . This common syndrome is...

Discontinuing AEDs

About half of all children with epilepsy will eventually outgrow their disorder. For patients who are seizure free for a period of time usually 2 years , a trial-off of AED is almost always reasonable. In this scenario, approximately 70 of children are successfully weaned from AEDs. Risk factors for recurrence of seizures after weaning AEDs include i onset of epilepsy during adolescence ii epileptiform discharges on EEG and iii symptomatic vs. idiopathic epilepsy syndrome 28 . While none of...

Interactions Epilepsia Drugs

Early identification of refractory epilepsy. N Engl J Med 2000 341 314-319. 2. Mohanraj R, Brodie MJ. Diagnosing refractory epilepsy response to sequential treatment schedules. Eur J Neurol 2006 13 277-282. 3. Perucca E. Pharmacoresistance in epilepsy how should it be defined CNS Drugs 1998 10 171-179. 4. Smith D, Defalla BA, Chadwick DW. The misdiagnosis of epilepsy and the management of refractory epilepsy in a specialist clinic. QJM 1999 92 15-23. 5. Devinsky O....

Impact On Behaviour And General Health

Reliable and valid behavioural outcome tools such as the aberrant behaviour checklist 42 are available, but are too complex to administer in a clinical rather than a research setting. Clinical practice is more likely to be driven by carer concerns and these are often influenced by the recent history of behaviour. Having established objective evidence of behavioural change, careful attribution of causation is necessary as this may be the result of numerous other factors including physical...

Zonisamide

In a preliminary report of patients with refractory primary generalized epilepsy 33 treated with ZNS, two of three patients with myoclonic seizures had a gt 50 reduction in seizures. On a database review of patients with JME treated with LTG, TPM and ZNS, four patients were on ZNS 70 . Generalized tonic-clonic seizures were substantially reduced, but myoclonic seizures increased in these patients on ZNS, while absence seizures remained unchanged. One retrospective study looked into the efficacy...

Disorders of vitamin b6 metabolism

Pyridoxal 5'-phosphate PLP is the B6 vitamer, which has co-factor activity and acts with several enzymes that are involved in the metabolism of neurotransmitters e.g. dopamine, serotonin, glutamate and y-aminobutyric acid GABA . Progress in the understanding of Table 4.3 Non-epileptogenic paroxysmal disorders in infancy Table 4.3 Non-epileptogenic paroxysmal disorders in infancy Cardiogenic e.g. long Q-T syndrome Sandifer syndrome gastro-oesophageal reflux Benign paroxysmal torticollis in...

Specific Aeds For Specific Seizure Types And Epilepsy Syndromes

AEDs can be broadly grouped into three categories narrow spectrum, broad spectrum, and syndrome-specific Table 5.1 . In general, partial epilepsies may be treated with either narrow- or broad-spectrum AEDs. However, broad-spectrum AEDs are usually required for generalized or mixed epilepsy syndromes. Beyond the spectrum of action, selection of an AED also depends on the medicine's formulation - is the child able to swallow liquid, sprinkles or pills Table 5.2 Special consideration of the...

Comparison Of New And Old Aeds Randomized Controlled Studies of New AEDs

The largest study in epilepsy care has been the Standard and New Antiepileptic Drugs SANAD study, which was conceived as a pragmatic, prospective randomized study comparing efficacy and tolerability of standard treatment and new AEDs. Recruited patients were older than 4 years of age and were diagnosed as having epilepsy. Patients were recruited from a number of centres within the UK between December 1999 and August 2004, and were reviewed at 3, 6 and 12 months after randomization and at least...

End of battery life

One relative disadvantage of VNS therapy is that the lithium-titanium battery has a finite life span, and needs to be replaced. An end-of-life indicator is now built into the device, so that patients and physicians will be signalled during routine device checks if a battery replacement is required. This indicator will begin to display an end-of-battery-life message approximately 6 months before the battery is completely expended. Battery replacement should be performed before the battery is...

Therapeutic Monitoring With Serum Aed Levels

Measuring AED concentrations is important in epilepsy management for two reasons i assessment of compliance and ii ascertaining toxicity. Monitoring AED levels becomes even more important in the aged because older patients may have memory problems or fail to comply with the drug regimen. Pharmacokinetic changes associated with advanced age include variable absorption, reduced renal and hepatic clearance and reduced serum albumin, which may contribute to more variability in the relationship...

Ruling Out Pseudoresistance

'Pseudoresistance', in which seizures persist because the disorder has not been adequately or appropriately treated, must be excluded or corrected before AED treatment can be declared as having failed 3 . It may arise in a number of situations Table 8.1 , of which misdiagnosis of epilepsy is probably one of the most common. Conditions that frequently mimic epileptic seizures include vasovagal syncope, cardiac arrhythmias and metabolic disturbances 4 . Pseudoseizures or non-epileptic psychogenic...

Drugs Of First Choice And Second Choice And Thirdline Antiepileptic Drugs In Children

It should be ascertained in every child with medically refractory seizures that the drugs of first choice have been tried. For a discussion of drug choices related to seizure type and syndrome, see Chapter 5. In the daily practice of treating patients with seizures, one cannot avoid the process of selecting the next drug if the current drug is failing, even if satisfactory scientific evidence to support the choice is lacking. Accordingly, Table 6.3 provides data on which drugs have class I, II...

Clinical evidence of synergistic combinations

The most scientifically valid approach to study such potential interactions is the isobolographic method Figure 8.2 , in which two AEDs are given in various dose proportions to identify the most effective regimen in terms of seizure control 34 . This approach has been successfully applied in animal studies 35 , but presents logistic difficulties in the clinical trial setting because of the wide inter-individual variation in the pharmacokinetics and pharmacodynamics of different AEDs. The ideal...

International League Against Epilepsy Guidelines Newly Diagnosed Epilepsy

According to the ILAE guidelines, the absence of class I and class II randomized controlled trials RCTs for children with absence seizures implies a marked deficiency in adequately powered, seizure type-specific, published studies for this category, and no AEDs reach the highest level of evidence level A or B for efficacy effectiveness for children with absence seizures level C . Table 11.3 Recommendations on treatment of specific IGE syndromes in AAN and ILAE guidelines AAN new AEDs in newly...

Taking A History In A Patient With SeizUres And Epilepsy

Seizures Work Algorithm

Treatment of newly diagnosed epilepsy begins with accurate diagnosis and appropriate seizure classification Figure 5.1 . A detailed history is essential, complemented by electroencephalography testing and neuroimaging in many cases. Elements of the history, Ren e A. Shellhaas, MD, Division of Pediatric Neurology, C. S. Mott Children's Hospital, University of Michigan, Ann Arbor, Michigan, USA Dennis J. Dlugos, MD, MSCE, Associate Professor, Division of Neurology, The Children's Hospital of...

Common Clinical Practice

In spite of poor-quality data, when treating patients with IGE, the possibility of seizure aggravation induced by AEDs has to be considered. It is critical to make a correct syndromic diagnosis and identify all seizure types. If this is not possible, a broad-spectrum AED should be used. Patients with multiple seizure types seem to be especially prone to seizure aggravation 74 . Drugs that block Na channels, in addition to GABA-ergic drugs, may exacerbate absence and myoclonic seizures, so they...

Introduction

Perhaps uniquely compared with other groups, epilepsy has a pervasive impact across the lives of people with intellectual disabilities IDs . Studies suggest that as many as one-fifth of the population of people with intellectual disabilities across the lifespan have epilepsy 1 . Higher prevalence figures are quoted in institutional settings and with decreasing intelligence quotient IQ 2-4 . This population will often have complex epilepsy which can be difficult to treat due to its severity but...

Valproate

Valproate has been available since the 1970s, but remains the first-line drug for many epilepsy syndromes, including juvenile myoclonic epilepsy and syndromes associated with absence seizures. Valproate may be the only effective agent for some patients. A recent large randomized open-label trial demonstrated superior efficacy compared with lamotrigine, and superior tolerability compared with topiramate, in adults and children with idiopathic generalized or unclassified epilepsy 16 . Seizure...

Is Aed Treatment Indicated After The First Unprovoked Seizure The First Trial Group

Although studies of seizure recurrence have quantified the risk of and identified risk factors associated with further seizures, the impact of AED treatment on the natural history of early epilepsy remains to be clarified. None of the currently available AEDs have displayed convincing anti-epileptogenic properties, and are perhaps more accurately described as anti-seizure drugs. Whether a purely symptomatic effect of preventing seizures would alter the natural course of the epilepsy is a moot...

P

Stimulation 53, 140 paediatric dosing ranges, AEDs 93-5 palliative surgery 44 pancreas transplantation 221-2 pancreatitis, valproate therapy 7-8 panic, ictal 292 panic disorder 291 pharmacotherapy 292-3 prevalence 282 parasomnias 105 parkinsonian symptoms, as side-effect of AEDs 179 Parkinson's disease, polytherapy 140-1 paroxetine 285 drug interactions 286-7 paroxysmal disorders in infancy 66 paroxysmal dystonias 104 partial epilepsy 10, 12, 13, 15 AED treatment in children 89, 90, 95, 109...

Monotherapy Vs Combination Therapy

In the child whose seizures are resistant to treatment, the question almost invariably arises as to whether combination therapy might be superior to sequential monotherapies. The rationale for polytherapy is based on the assumption that AEDs interact synergistically and that multiple drugs can provide more seizure protection together than one drug alone. However, combining drugs can produce more side-effects than administering one drug alone. More recently, the concept of monotherapy and...

Seizure Aggravation

Whether at the time of initiation of anti-epileptic therapy, or in the patient whose seizures have not yet yielded to therapy, it is always important to keep in mind that AEDs may paradoxically worsen seizure frequency or induce new seizure types 25 . This is more common in the epilepsies of childhood than in adult patients, and more common with generalized epilepsies than with focal epilepsies. Many AEDs have been shown to occasionally be the cause of seizure exacerbation. The mechanisms by...

Pharmacokinetic And Pharmacodynamic Interaction Between Lithium And Aeds

There does not appear to be substantial risk for pharmacokinetic interactions between lithium and AEDs. Prior to the discovery of the mood-stabilizing properties of AEDs, lithium was the mood-stabilizing agent par excellence. Today, while many AEDs such as valproic acid, carbamazepine and lamotrigine have replaced the use of lithium in the management of bipolar patients, lithium continues to play an important role, above all, in patients with more refractory bipolar disease. It is not...

Ns stimulants

These are the first choice for therapy of ADHD. Methylphenidate and amphetamine compounds remain the most commonly used stimulants. Their safety and efficacy have been well established and they work in a dose-dependent manner. Their effectiveness in controlling symptoms has varied according to different trials from as high as 68-80 in children to 30-50 in children and adults 28 to 70 in adolescents . Our preference is to start with methylphenidate in its immediate-release formulation to...

Severe Myoclonic Epilepsy In Infancy Dravet Syndrome

Severe myoclonic epilepsy in infancy SMEI , first described by Dravet, is an early-onset epilepsy syndrome with catastrophic course and poor seizure as well as cognitive outcome. Onset is in the first year of life. Developmentally normal infants present with atypical febrile convulsions focal features, prolonged and episodes of febrile as well as afebrile status epilepticus. The occurrence of afebrile multiple type seizures including myoclonus from the second year of life onwards is accompanied...

Anticipatory Guidance Safety Precautions

Children with epilepsy are at risk for seizure-induced accidents and injuries. At the time of diagnosis, families should be reminded of several basic safety guidelines. It is practical to suggest that care-givers of children with epilepsy should be instructed in basic cardiopulmonary resuscitation. In order to minimize the risk of drowning, people with epilepsy should not bathe or swim alone. When swimming, the child should be supervised by an adult who is capable of assisting in the event of...

Benzodiazepines

Available benzodiazepines for chronic use include clonazepam, clorazepate and clobezam. Most benzodiazepines are not good choices for long-term therapy and should not be used as first-line agents. Patients may develop tolerance to the therapeutic effects of many of the benzodiazepines. Seizures may initially be decreased, but as tolerance develops over time, seizures may recur, necessitating dosage increases to regain control. Among the available benzodiazepines, clobezam has been touted as...