The long-term prognosis of epilepsy

294 Pages·2011·0.55 MB·English

by  Neligan, A.

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THE LONG-TERM PROGNOSIS OF EPILEPSY
AIDAN NELIGAN
UCL Institute of Neurology
Queen Square
London WC1N 3BG
A thesis submitted to University College London for the degree of
Doctor of Philosophy 2011.
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Declaration
I, Aidan Neligan, confirm that the work presented in this thesis is my own. Dr Gail Bell
calculated the standardised mortality ratios (SMRs) and the standardised incidence rates
(SIRs) for the NGPSE study and reproduced the Kaplan-Meier graphs in Stata after I
produced the original graphs in SPSS. Where information has been derived from other
sources, I confirm that this has been indicated in the thesis.
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Abstract
The five studies presented in this thesis consider different aspects of the long-term
prognosis of epilepsy and febrile seizures. The studies were:
1). A systemic review to examine a) how the risk of premature mortality in an individual
with epilepsy changes over time and b) whether population mortality rates due to epilepsy
have changed over time. (Study 1)
2). An extension of the National General Practice Study of Epilepsy (NGPSE), a
prospective community-based incident cohort study to examine a) long-term seizure
prognosis and mortality in people with epilepsy and b) seizure prognosis in children with
febrile seizures (Study 2)
3). Two retrospective hospital-based cohort studies examining prognosis of chronic
epilepsy with regard to a) frequency of different seizure patterns (Study 3) and medium-
term seizure outcome following anti-epileptic drug changes (Study 4).
4). Asystematic review examining the impact of aetiology and others factors on outcome in
status epilepticus (Study 5).
Amongst the findings were:
1): There is no conclusive evidence that either the overall standardised mortality ratio
(SMR) or the mortalityrate of people with epilepsy has changed significantly over time.
The SMR is highest soon after diagnosis and subsequently decreases with a possible late
increase after 10 years. In the NGPSE cohort the SMR remains significantly elevated after
20 years despite over 80% currently being in terminal remission.
2): 6.7% (95% CI 4, 11%) of children with febrile seizures developed epilepsy after 20
years.
3): Approximately one-third of people with chronic epilepsy have a history of at least one
significant period of seizure freedom (two or more years) while a comparable number with
apparent drug-resistant epilepsy attain at least one year of seizure freedom after medication
change, although approximately half subsequently relapse.
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4). Aetiology and, to a lesser extent, age are the primary determinants of prognosis in status
epilepticus.
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TABLE OF CONTENTS
Declaration............................................................................................................................2
Abstract.................................................................................................................................3
Table of contents..................................................................................................................5
List of tables and figures...................................................................................................12
Figures.................................................................................................................................14
Acknowledgements.............................................................................................................16
Publications......................................................................................................................... 17
Chapter 1: Introduction and literature review...............................................................19
1.1 Introduction..........................................................................................................19
1.1.1 Definitions....................................................................................................21
1.2 Incidence studies..................................................................................................23
1.2.1 Incidence of epilepsy in more developed countries.....................................24
1.3 Prevalence............................................................................................................29
1.3.1 Prevalence in developed countries...............................................................29
1.4 Risk factors for epilepsy.......................................................................................32
1.4.1 Neoplasms....................................................................................................33
1.4.2 Stroke...........................................................................................................33
1.4.3 Neurodegenerative disorders........................................................................35
1.4.4 Trauma.........................................................................................................35
1.4.5 Seizures and bacterial meningitis/encephalitis.............................................37
1.4.6 Seizures and other CNS infections and infestations....................................38
1.4.7 Learning disability and cerebral palsy.........................................................39
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1.5 Prognosis..............................................................................................................41
1.5.1 Recurrence after a single seizure..................................................................41
1.5.2 Recurrence after a second seizure................................................................42
1.5.3 Short and medium term prognosis...............................................................43
1.5.4 Long -term prognosis...................................................................................43
1.5.5 Prognostic factors.........................................................................................46
1.5.6 The impact of aetiology on prognosis..........................................................47
1.5.7 The impact of anti-epileptic drugs on prognosis..........................................48
1.5.8 Prognosis following AED withdrawal.........................................................50
1.5.9 Patterns of relapse and remission in epilepsy..............................................52
1.5.10 The prognosis for those with intractable epilepsy........................................53
1.6 Mortality...............................................................................................................56
1.6.1 Methodological issues..................................................................................56
1.6.2 Mortality following a newly diagnosed seizure...........................................58
1.6.3 Mortality in cohort studies...........................................................................59
1.6.4 Temporal trends in mortality in people with epilepsy.................................59
1.6.5 The impact of age and gender on mortality.................................................60
1.6.6 Causes of mortality......................................................................................61
1.6.7 Epilepsy-related deaths................................................................................63
1.6.7.1 SUDEP.....................................................................................................63
1.6.7.2 Accidents..................................................................................................64
1.6.7.3 Drowning.................................................................................................65
1.6.7.4 Suicide......................................................................................................65
1.6.8 Mortality and surgery...................................................................................65
1.6.9 Anti-epileptic drugs and mortality...............................................................66
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1.6.10 Conclusions..................................................................................................67
1.7 Febrile Seizures....................................................................................................68
1.7.1 Mortality and febrile seizures......................................................................69
1.7.2 Risk of subsequent epilepsy.........................................................................70
1.7.3 Conclusions..................................................................................................72
1.8 Status epilepticus..................................................................................................74
1.8.1 Introduction..................................................................................................74
1.8.2 Definition.....................................................................................................75
1.8.3 The epidemiology of status epilepticus........................................................77
Chapter 2: Aims.................................................................................................................81
2.1 Aims of the Systematic Review of the Temporal Trends in Mortality in People
with Epilepsy (Study 1)........................................................................................81
2.2 Aims of this extension to the National General Practice Study of Epilepsy and
Epileptic Seizures (NGPSE)(Study 2) ...............................................................82
2.3 Aims of the Seizure Patterns in Chronic Epilepsy Study (Study 3).....................83
2.4 Aims of the Impact of Medication Change in peoplewith Chronic Epilepsy Study
(Study 4)...............................................................................................................84
2.5 Aims of the Systematic Review of the Prognosis of Status Epilepticus (Study 5)..
..............................................................................................................................85
Chapter 3: The Systematic Review of the Temporal Trends in Mortality in people
with epilepsy (Study 1)...............................................................................86
3.1 Methods................................................................................................................86
3.2 Changes in SMR in people with epilepsy over the course of the condition........87
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3.2.1 Population-based cohort studies...................................................................87
3.2.2 Hospital-based studies..................................................................................93
3.2.3 Studies from institutions..............................................................................94
3.3 Population-based mortality trends in people with epilepsy.................................96
Chapter 4: Extension of the National General Practice Study of Epilepsy (NGPSE)
(Study 2)......................................................................................................98
4.1 Methods................................................................................................................98
4.1.1 Study design.................................................................................................98
4.1.1.1 Participants...............................................................................................98
4.1.1.2 Classification............................................................................................98
4.1.1.3 Initial follow-up.....................................................................................100
4.1.1.4 Ethical approval.....................................................................................100
4.1.2 Data protection and the implications for the NGPSE................................101
4.1.2.1 PIAG and the NGPSE............................................................................101
4.1.2.2 The Office of National Statistics (ONS) and the NGPSE......................104
4.1.2.3 Research & Development Departments.................................................104
4.1.2.4 Scotland and the NGPSE.......................................................................105
4.1.3 Current follow-up.......................................................................................106
4.1.3.1 Mortality analysis...................................................................................106
4.1.3.2 Mortality statistical analysis: statistical analysis....................................107
4.1.3.3 Febrile seizures statistical analysis.........................................................108
4.2 Results................................................................................................................109
4.2.1 The long-term risk of mortality in people with epilepsy.............................109
4.2.2 Follow-up of seizure outcome.....................................................................119
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4.2.3 The long-term prognosis of people with febrile seizures............................121
4.2.4 Thelong-term prognosis of people with epilepsy......................................125
4.2.4.1 Survival analysis of time to first seizure and Cox regression model.....129
4.2.4.2 The impact of aetiology on prognosis in definite epilepsy....................133
Chapter 5: The Study of Seizure Patterns in people with chronic epilepsy (Study 3)
....................................................................................................................137
5.1 Methods..............................................................................................................137
5.1.1 Participants.................................................................................................137
5.1.2 Seizure patterns:.........................................................................................137
5.1.3 Seizure and syndrome classification:.........................................................138
5.1.4 Ethical approval:........................................................................................139
5.1.5 Statistical analysis......................................................................................139
5.2 Results................................................................................................................140
Chapter 6: The Study of the Impact of Medication change in People with Chronic
Epilepsy (Study 4)....................................................................................145
6.1. Methods..............................................................................................................145
6.2 Results................................................................................................................147
Chapter 7: The Systematic Review of the Prognosis of Convulsive Status
Epilepticus (Study 5)................................................................................154
7.1 Methods: search criteria.....................................................................................154
7.2. Major aetiologies in status epilepticus...............................................................156
7.3 Frequency and prognosis of different aetiologies..............................................161
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7.3.1 Stroke and status epilepticus......................................................................161
7.3.2 Alcohol, substance abuse and drug-induced status epilepticus..................164
7.3.3 Status epilepticus and antiepileptic drug reduction or withdrawal or low
antiepileptic drug levels.............................................................................165
7.3.4 Severe acute cerebral anoxia/hypoxia and status epilepticus.....................167
7.3.5 CNS infections, encephalitis and status epilepticus...................................168
7.3.6 Cerebral Tumour and status epilepticus.....................................................171
7.3.7 Trauma and status epilepticus....................................................................171
7.3.8 Metabolic disorders and status epilepticus.................................................172
7.3.9 Cryptogenic status epilepticus...................................................................173
7.4 Other prognostic factors in SE...........................................................................176
7.4.1. The duration of status epilepticus and its relation to outcome...................176
7.4.2 EEG and prognosis of SE:.........................................................................180
7.4.3 GCS on admission:.....................................................................................183
7.4.4 Age:............................................................................................................185
7.4.4.1 Status epilepticus in children:................................................................185
7.4.4.2 Status epilepticus in adults.....................................................................187
7.5 Outcome measures in status epilepticus.............................................................191
7.4.1 Mortality and status epilepticus.................................................................191
7.4.2 Morbidity -neurological deficit and status epilepticus..............................192
7.4.3 Morbidity –neuro-cognitive sequelae of status epilepticus.......................194
7.4.4 Morbidity -the risk of epilepsy after status epilepticus.............................195
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