Framing clinical questions and search for evidence
7. Surgery
Summary
One RCT in people who had been seizure free for at least 2 years found that further seizures were more likely if people stopped treatment than if they continued antiepileptic medi-cation. Clinical predictors of relapse after drug withdrawal included age, seizure type, number of AEDs being taken, whether seizures had occurred since AEDs were started, and the period of remission before drug withdrawal. There is a need to trade off between benefits and harms while attempt-ing to withdraw AEDs in seizure free individuals.
There is evidence to support waiting for at least two or more seizure free years before discontinuing AEDs in chil-dren, particularly if individuals have an abnormal EEG and partial seizures. There is insufficient evidence to establish when to withdraw AEDs in children with generalized seizures. There is no evidence to guide the timing of with-drawal of AEDs in seizure-free adults. The ideal duration over which the drugs should be tapered is not known.
4 Berg AT, Shinnar S. The risk of seizure recurrence following a first unprovoked seizure: a quantitative review. Neurology 1991;
41: 965–72.
5 Cockerell OC, Johnson AL, Sander JW, et al. Remission of epilepsy: results from the national general practice study of epilepsy. Lancet 1995; 346: 140–4.
6 Marson A, Jacoby A, Johnson A, Kim L, Gamble C, Chadwick D.
on behalf of the Medical Research Council MESS Study Group.
Immediate versus deferred antiepileptic drug treatment for early epilepsy and single seizures: a randomized controlled trial.
Lancet 2005; 365: 2007–13.
7 First Seizure Trial Group (FIRST Group). Randomized clinical trial on the efficacy of antiepileptic drugs in reducing the risk of relapse after a first unprovoked tonic clonic seizure. Neurology 1993; 43: 478–83.
8 Musicco M, Beghi E, Solari A, et al., for the FIRST Group.
Treatment of first tonic clonic seizure does not improve the prognosis of epilepsy. Neurology 1997; 49: 991–8.
9 Gilad R, Lampl Y, Gabbay U, Eshel Y, Sarova-Pinhas I. Early treatment of a single generalized tonic-clonic seizure to prevent recurrence. Arch. Neurol. 1996; 53: 1149–52.
10 Chandra B. First seizure in adults: to treat or not to treat. Clin.
Neurol. Neurosurg. 1992; 94(Suppl.): S61–3.
11 Camfield P, Camfield C, Dooley J, Smith E, Garner B. A random-ized study of carbamazepine versus no medication after a first unprovoked seizure in childhood. Neurology 1989; 39: 851–2.
12 Pauranik A. Short-term anti-epileptic therapy for single seizure cases. Epilepsia 1997; 38(Suppl. 3): 88.
13 Marson AG, Williamson PR, Hutton JL, et al. on behalf of the Epilepsy Monotherapy Trialists. Carbamazepine versus valproate monotherapy for epilepsy (Cochrane Review). The Cochrane Library, Issue 4. John Wiley & Sons, Ltd., Chichester, UK, 2003.
14 Tudur Smith C, Marson AG, Williamson PR. Carbamazepine versus phenobarbitone monotherapy for epilepsy (Cochrane Review). The Cochrane Library, Issue 4. John Wiley & Sons, Ltd., Chichester, UK, 2003.
15 Tudur Smith C, Marson AG, Clough HE, et al. Carbamazepine versus phenytoin monotherapy for epilepsy (Cochrane Review). The Cochrane Library, Issue 4. John Wiley & Sons, Ltd., Chichester, UK, 2003.
16 Taylor S, Tudur Smith C, Williamson PR, et al. Phenobarbitone versus phenytoin monotherapy for partial onset seizures and generalized onset tonic-clonic seizures (Cochrane Review). The Cochrane Library, Issue 4. John Wiley & Sons, Ltd., Chichester, UK, 2003.
17 Tudur Smith C, Marson AG, Williamson PR. Phenytoin versus valproate monotherapy for partial onset seizures and general-ized onset tonic-clonic seizures (Cochrane Review). The Cochrane Library, Issue 4. John Wiley & Sons, Ltd., Chichester, UK, 2003.
18 Posner EB, Mohamed K, Marson AG. Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents (Cochrane Review). The Cochrane Library, Issue 1.
John Wiley & Sons, Ltd., Chichester, UK, 2006.
19 Marson AG, Kadir ZA, Hutton JL, et al. Gabapentin add-on for drug-resistant partial epilepsy (Cochrane Review). The Cochrane Library, Issue 4. John Wiley & Sons, Ltd., Chichester, UK, 2003.
20 Chaisewikul R, Privitera MD, Hutton JL, et al. Levetiracetam add-on for drug-resistant localization related (partial) epilepsy (Cochrane Review). The Cochrane Library, Issue 4. John Wiley &
Sons, Ltd., Chichester, UK, 2003.
21 Ramaratnam S, Marson AG, Baker GA. Lamotrigine add-on for drug-resistant partial epilepsy (Cochrane Review). The Cochrane Library, Issue 4. John Wiley & Sons, Ltd., Chichester, UK, 2003.
22 Castillo S, Schmidt DB, White S. Oxcarbazepine add-on for drug-resistant partial epilepsy (Cochrane Review). The Cochrane Library, Issue 4. John Wiley & Sons, Ltd., Chichester, UK, 2003.
23 Pereira J, Marson AG, Hutton JL. Tiagabine add-on for drug-resistant partial epilepsy (Cochrane Review). The Cochrane Library, Issue 4. John Wiley & Sons, Ltd., Chichester, UK, 2003.
24 Jette NJ, Marson AG, Hutton JL. Topiramate add-on for drug-resistant partial epilepsy (Cochrane Review). The Cochrane Library, Issue 4. John Wiley & Sons, Ltd., Chichester, UK, 2003.
25 Marson AG, Kadir ZA, Hutton JL, et al. The new antiepileptic drugs: a systematic review of their efficacy and tolerability.
Epilepsia 1997; 38: 859–80.
26 Kalviainen R, Nousiainen I, Mantyjarvi M, et al. Vigabatrin, a gabaergic antiepileptic drug, causes concentric visual field defects. Neurology 1999; 53: 922–6.
27 Chadwick DW, Marson AG. Zonisamide add-on for drug-resistant partial epilepsy (Cochrane Review). The Cochrane Library, Issue 4. John Wiley & Sons, Ltd., Chichester, UK, 2003.
28 Medical Research Council Antiepileptic Drug Withdrawal Study Group. Randomised study of antiepileptic drug with-drawal in patients in remission. Lancet 1991; 337: 1175–80.
29 Medical Research Council Antiepileptic Drug Withdrawal Study Group. Prognostic index for recurrence of seizures after remission of epilepsy. BMJ 1993; 306: 1374–8.
30 Sirven JI, Sperling M, Wingerchuk DM. Early versus late antiepileptic drug withdrawal for people with epilepsy in remis-sion (Cochrane Review). The Cochrane Library, Issue 1. John Wiley & Sons, Ltd., Chichester, UK, 2006.
31 Ranganathan LN, Ramaratnam S. Rapid versus slow with-drawal of antiepileptic drugs (Cochrane Review). The Cochrane Library, Issue 2. John Wiley & Sons, Ltd., Chichester, UK, 2006.
32 Cucherat M. [Meta-analysis of surgery trials in refractory epilepsy] Rev. Neurol. (Paris) 2004; 160(Spec. No. 1): 5S232–40 (in French).
33 Wiebe S, Blume WT, Girvin JP, et al. A randomized, controlled trial of surgery for temporal lobe epilepsy. N. Engl. J. Med. 2001;
345: 311–18.
34 Engel Jr J, Wiebe S, French J, et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons. Neurology 2003; 60: 538–47. [Erratum in: Neurology 2003; 60: 1396].
Chapter 18: Epilepsy 183
Background
Alzheimer disease (AD) is a degenerative brain disease that is the most common cause of dementia. Incidence and preva-lence increase exponentially with age through at least the ninth decade, with little evidence of a plateau at higher ages.
The prevalence of severe dementia in all persons older than age 60 is estimated to be 5%, and in those older than age 85 it is estimated to be 20% to 50%. The lifetime risk of AD is esti-mated at 12% to 17% [1]. With more people living longer, the prevalence of AD is increasing. Since 1980, the number of Americans with AD has doubled to 4.5 million and may triple by 2050 [2]. Prevalence estimates of the co-occurrence of dementia and Parkinsonism vary widely among studies but average 20% to 30%; annual incidence rates of dementia in established Parkinsonism also vary but average 5% to 6% [3].
Statistics for other forms of dementia are less precise, but fron-totemporal dementia is probably about one-tenth as common as AD. Vascular changes are common in dementia patients, but the frequency of mixed vascular-degenerative dementia – especially AD – is much more common than ‘pure’ vascular dementia (VaD).
Although most cases of AD occur after age 60, about 5%
are early-onset familial cases related to one of three autoso-mal dominant mutations. Early-onset familial AD typically strikes young persons ranging in age from the mid-thirties to the mid-fifties. To date, three separate genetic mutations have been identified that may cause early-onset familial AD, and all three are inherited in an autosomal dominant pattern. The most common mutation thought to account for most of the autosomal dominant kindreds is presenilin-1 [4], and it is the only one of the three for which there is currently a com-mercially available genetic test. The other two include the amyloid precursor protein gene on chromosome 21 [5] and presenilin-2 on chromosome 1 [6]. All result in increased con-centrations of abeta-amyloid, which underscores the patho-genic importance of abeta-amyloid in the evolution of AD [7].
The genetic risk factor that accounts for more cases of AD than any other, however, is the apolipoprotein E e4 allele
located on chromosome 19. The apolipoprotein E e4 allele is associated with late-onset familial and ‘sporadic’ AD, not autosomal dominant early-onset familial AD [8]. The preva-lence of the apolipoprotein E e4 allele varies worldwide but is about 20% in North America [9].
Dementia imposes an immense burden on families, because 70% of these patients are cared for at home [10]. The cost of care averages $42,000 annually [11], so reducing the financial as well as the medical burden of AD is a major goal of medical diagnosis and management. Parkinsonism further adds to the cost of care. These statistics primarily reflect that most AD patients are retirees and do not account for the few patients who lose years of work productivity because of early-onset AD. The statistics also do not account for potentially reversible conditions mistaken for AD or for the increased medical bur-den of stress-related illness in caregivers.
Treatment of AD and other forms of dementia primarily focuses on symptoms. Nearly all therapeutic trials have been conducted in patients with AD, with results extrapolated, cor-rectly or not, to other etiologic categories. There is little evidence-based support for any putative prevention therapy;
approaches that have shown disappointing results in con-trolled clinical trials include oestrogen replacement [12], non-steroidal anti-inflammatory drugs [13], and vitamin E [14].
Intellectual impairment benefits modestly from cholinesterase inhibitor therapy [15] in mild to moderate AD and memantine hydrochloride therapy in moderate to severe AD [16].
Behavioural management includes the control of psychosis and agitation. Although atypical antipsychotic drugs have gained widespread use in this regard, they lack approval from the US Food and Drug Administration for this specific use. In 2005, the Food and Drug Administration required a black box warning label on atypical antipsychotics used to treat elderly patients with dementia because of unpublished data suggest-ing an increased risk of mortality (http://www.fda.gov/cder/
drug/advisory/antipsychotics.htm). Other important aspects of management are lifestyle changes (e.g. driving restrictions [17]), caregiver burnout [18], and assisted living, legal guardianship, and related interventions.
C H A P T E R 1 9
Dementia treatment: let the evidence lead us
Bart M. Demaerschalk, Bryan K. Woodruff, Richard J. Caselli
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Many controversies and uncertainties about the pathogen-esis, diagnosis, and treatment of AD confront the clinician and scientist and will continue to do so until mechanistic insights translate into more effective clinical therapeutics. Evidence will always be an important cornerstone of therapy, but it is especially vital as long as therapeutic inefficacy fosters the proliferation of witch doctors and snake-oil purveyors.