Has the mortality of status epilepticus changed over the past few decades?

Earlier and more aggressive treatment of status epilepticus has long been established orthodoxy. In addition to increasing therapeutic options, it is of critical importance to understand whether or not this has translated into improved prognosis. In this review, we examine the evidence as to whether the mortality of convulsive status epilepticus changed over the past few decades. In particular, we discuss a recent systematic review and meta-analysis examining this question and its implications. We discuss potential reasons why there is no evidence of improved prognosis in terms of mortality and ways in which this may be addressed. Finally, we advocate the urgent need for accurate data on functional outcomes in non-fatal cases of status epilepticus. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.

The impact of a clinical review of people with active epilepsy not under shared care by a GP with special interest.

PURPOSE: To review clinical outcomes of a single face-to-face review of people with epilepsy (PWE) not under shared care, and any recommendations following a notes review of non-attendees and those under shared care, by a GP with Special Interest in epilepsy (GPwSIe). METHOD: One hundred and eighty one PWE, not under shared care were invited for a review. In addition, fifty six people under shared care had a notes review. Interventional outcomes were reviewed after 12 months. RESULTS: There had been ten deaths (all non-attributable to epilepsy), and six people had left the area, leaving 221 people who completed the audit. Fifty one percent attended for review, and were more likely to be in documented remission (p = 0.01). The frequency of annual GP epilepsy reviews in the following year did not rise significantly. There was a significant rise in vitamin D prescriptions (p < 0.001). Thirty seven DEXA scans were arranged, 76% were abnormal. There was reluctance by patients to withdraw medication, change multi dose, or subtherapeutic anti-seizure medication (ASM) regimes, even in the context of long-term seizure remission or inadequate seizure control. Three people achieved remission from changes made to ASM as a result of the review. CONCLUSION: Review of PWE in primary care remains poor. Attitudes from both GPs and PWE to their condition needs evaluation in order to plan future care. Bone health is an issue easily addressed in primary care and should be promoted through education or the re-introduction of a specific QOF (Quality and Outcomes Framework) target. Guidance on bone health for ASM needs clarification. This study adds to the evidence of the effectiveness of a GPwSIe.

CIDP: mimics and chameleons.

The diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is usually straightforward, but atypical presentations can represent a significant diagnostic challenge. This review highlights the clinical and electrophysiological 'red flags' that should make one consider an alternative diagnosis.

The incidence and prevalence of epilepsy in the United Kingdom 2013-2018: A retrospective cohort study of UK primary care data.

PURPOSE: The aim of this study was to update overall incidence and prevalence calculations for epilepsy of the United Kingdom (UK) and its constituent nations (England, Northern Ireland, Scotland, and Wales). METHODS: We used data from primary care practices contributing to the Clinical Practice Research Datalink (CRPD), based on the electronic health records of 14 million patients, representing approximately 20% of the population. CPRD contains data from two different health record systems: the Vision clinical system (CPRD GOLD database) and the EMIS Web® clinical system (CPRD Aurum database). We calculated incidence and prevalence rates with 95% confidence intervals (CIs). Data were stratified by age, gender, deprivation, country (England, Scotland, Wales and Northern Ireland) and region (England only). RESULTS: In the UK, the estimated overall point prevalence for epilepsy was 9.37 per 1000 persons / year (95% CI 9.34-9.40) and the overall estimated incidence rate was 42.68 per 100,000 person-years (95% 42.18-43.18) using the CPRD GOLD database. In England, the estimated incidence (37.41 (95% CI 36.96-37.83)) and prevalence (8.85 (95% CI 8.83-8.87)) was lower (combined databases) compared to figures for Scotland (incidence 47.76 (95% CI 46.15-49.42)); prevalence 10.13 (95% CI 10.06-10.20)) (CPRD GOLD only), Wales (incidence 54.84 (95% CI 52.79-56.95); prevalence 11.40 (95% CI 11.31-11.49)) (CPRD GOLD only) and Northern Ireland (incidence 46.18 (95% CI 43.13-49.90); prevalence 12.08 (95% CI 11.93-12.23))(combined databases). Prevalence and incidence were higher in more deprived regions. CONCLUSION: The prevalence and incidence of epilepsy in the UK is broadly in line with other high income countries, showing the usual pattern of high incidence in the young and the old, with a nadir in middle age. The prevalence of epilepsy has fallen slightly since 2011. There is significant geographical variation (between countries and between regions), and a suggestion of a relationship between deprivation and epilepsy which needs further investigation.

Is a separate clinical pathway for first seizures justified? Appraisal of the first seizure pathway at a tertiary neuroscience centre.

OBJECTIVES: To investigate the clinical characteristics, final diagnosis, investigation results, management, response to anti-seizure medications (ASMs) and clinical outcomes of individuals assessed in a First Seizure service over a 5-year period. METHODS: Retrospective analysis of 772 individuals who were clinically assessed in a dedicated First Seizure service at National Hospital for Neurology & Neurosurgery (NHNN), Queen Square over a 5-year period. RESULTS: 772 individuals were assessed following a suspected or reported first seizure (median age of 54, average age of 39.4, range 16-96). 393 (50.9 %) were ultimately diagnosed with a definite seizure of which 183 (46.5 %) had experienced seizures previously which had not been recognised or diagnosed. 250 (32 %) had vasovagal syncope and 69 (18.2 %) were diagnosed with psychogenic non-epileptic seizures. EEGs in 16.6 % of individuals who had a first unprovoked seizure demonstrated epileptiform discharges, whilst 33.6 % had abnormal MRI findings felt to be clinically relevant. CONCLUSIONS: Seizure mimics represent a significant proportion of attendees to a 'first seizure' service. Improved recognition and more education of this issue could facilitate earlier management of these other diagnostic entities and ensure that only appropriate cases are referred to the first seizure service. Almost half of 'first seizure' cases had previous seizures, highlighting the importance of obtaining this relevant history and in reviewing ASM-naive individuals in a timely manner with the primary aim of preventing further recurrences.

A review of nerve conduction studies in cases of suspected compression neuropathies of the upper limb.

INTRODUCTION: Entrapment neuropathies, particularly those affecting upper limbs, are common reasons for referral for nerve conduction studies (NCS). However, concordance between clinical findings and NCS findings, especially in patients being considered for intervention including decompressive surgery, has not been assessed. METHODS: We conducted a retrospective study using records from a tertiary referral centre's neurophysiology database. We aimed to establish the proportions of agreement between the suspected clinical diagnosis as defined by the referring clinician and NCS findings in the setting of an upper limb entrapment neuropathy. RESULTS: Of the 571 referrals for NCS, suspected bilateral carpal tunnel syndrome was the commonest reason for referral (30.5%). In total, there was 51.5% concordance between suspected clinical diagnosis and NCS findings. Patients with NCS evidence of an entrapment neuropathy (n = 437) were more likely to be older compared to those with normal studies (54.0 +/- 15.6 years vs. 45.9 +/- 13.4 years, p < 0.001). Those with normal NCS findings were more likely to be female (72%, p = 0.001). An alternative or additional diagnosis was found in 14%. CONCLUSION: This study raises concerns regarding the appropriateness of referral for decompressive surgery based on clinical diagnosis alone as many have an additional or alternative diagnosis as suggested by NCS findings.

Aetiology and prognosis of encephalopathic patterns on electroencephalogram in a general hospital.

The purpose of this study was to investigate the frequency and clinical outcome of patients with encephalopathic electroencephalograms (EEGs) in a neurophysiology department based in a general hospital. We performed a retrospective review of all EEGs obtained during an 18-month period in a large tertiary referral hospital. The referral reasons for EEG, the diagnoses reached, and patient outcomes were reviewed according to EEG severity. One hundred and twenty-three patients with encephalopathic EEGs were reviewed. The most common referral reason found was for an assessment of a possible first-onset seizure. The most common diagnosis found was one of dementia or learning disability. Of patients who were followed-up for a median of 19 months, 20.7% had died. The mortality rate generally increased according to the severity of the encephalopathy on EEG. However, 21.4% of those patients with excessive theta activity only on EEG had died. This study highlights an increased mortality even in the apparently 'milder' degrees of EEG abnormalities.

Non-traumatic brachial plexopathies, clinical, radiological and neurophysiological findings from a tertiary centre.

OBJECTIVE: To establish the clinical characteristics, aetiology, neuro-physiological characteristics, imaging findings and other investigations in a cohort of patients with non-traumatic brachial plexopathy (BP). METHODS: A 3-year retrospective study of patients with non-traumatic BP identified by electromyography (EMG) and nerve conduction studies (NCS). Clinical information was retrieved from patients' medical charts. RESULTS: Twenty-five patients were identified. Causes of BP included neuralgic amyotrophy (NA) (48%), neoplastic (16%), radiation (8%), post infectious (12%), obstetric (4%), rucksack injury (4%), thoracic outlet syndrome (4%) and iatrogenic (4%). Patients with NA presented acutely in 50%. The onset was subacute in all others. Outcome was better for patients with NA. All patients with neoplastic disease had a previous history of cancer. MRI was abnormal in 3/16 patients (18.8%). PET scanning diagnosed metastatic plexopathy in two cases. CONCLUSIONS: NA was the most common cause of BP in our cohort and was associated with a more favourable outcome. The authors note potentially discriminating clinical characteristics in our population that aid in the assessment of patients with brachial plexopathies. We advise NCS and EMG be performed in all patients with suspected plexopathy. Imaging studies are useful in selected patients.

A study of idiopathic generalised epilepsy in an Irish population.

UNLABELLED: Idiopathic generalised epilepsy (IGE) is subdivided into syndromes based on clinical and EEG features. PURPOSE: The aim of this study was to characterise all cases of IGE with supportive EEG abnormalities in terms of gender differences, seizure types reported, IGE syndromes, family history of epilepsy and EEG findings. We also calculated the limited duration prevalence of IGE in our cohort. METHODS: Data on abnormal EEGs were collected retrospectively from two EEG databases at two tertiary referral centres for neurology. Clinical information was obtained from EEG request forms, standardised EEG questionnaires and medical notes of patients. RESULTS: two hundred twenty-three patients met our inclusion criteria, 89 (39.9%) male and 134 (60.1%) females. Tonic clonic seizures were the most common seizure type reported, 162 (72.65%) having a generalised tonic clonic seizure (GTCS) at some time. IGE with GTCS only (EGTCSA) was the most common syndrome in our cohort being present in 94 patients (34 male, 60 female), with 42 (15 male, 27 female) patients diagnosed with Juvenile myoclonic epilepsy (JME), 23 (9 male, 14 female) with Juvenile absence epilepsy (JAE) and 20 (9 male, 11 female) with childhood absence epilepsy (CAE). EEG studies in all patients showed generalised epileptiform activity. CONCLUSIONS: More women than men were diagnosed with generalised epilepsy. Tonic clonic seizures were the most common seizure type reported. EGTCSA was the most frequent syndrome seen. Gender differences were evident for JAE and JME as previously reported and for EGTCSA, which was not reported to date, and reached statistical significance for EGTCA and JME.

A review of people who did not attend an epilepsy clinic and their clinical outcomes.

PURPOSE: To review the clinical outcomes of people who failed to attend or failed subsequent follow up in a Primary Care based specialist epilepsy service. METHOD: The case notes of 200 people who had failed to initially attend the service or subsequent follow up from 2005 to 2013 were reviewed. RESULTS: Clinical outcomes were determined for 152 people, with the remaining 48 having left the area. For those not attending at all, 64% had no further recorded events, a further 22% came under alternative specialist care and were managed appropriately, 6% were already in remission at the time of referral or at follow up and stayed seizure free. For people attending, but were subsequently lost to follow up, 78% were in remission, had improved seizure frequency, and normal pregnancies. In total 6% of those with poor control came under subsequent Neurological care. CONCLUSION: This study suggests that for the majority of people who fail to attend or are lost to follow up in a primary care specialist epilepsy clinic, the primary reasons appear to be that they had no further events, improved seizure control or that seizure remission has been achieved. The majority with persistent poor control came under Neurological care.

Management of epilepsy in the community.

We posted a questionnaire on epilepsy to all 375 GPs in Cork and Kerry (population 500,000) The questionnaire consisted of 10 sections, covering areas like GP demographics, initial referral practice following a first seizure, advice given to patients and GP's attitudes towards patients with epilepsy. The main focus of the study was GP awareness of 7 of the newer anti-epileptics and their side effects. There was a response rate of 46.7% (175) and revealed that the majority (87%) initially refer patients to a neurologist for further assessment. The majority of GPs gave patients advice about driving, AED side effects, interaction with the OCP and pregnancy counselling. GP awareness of the newer anti-epileptics is very variable with Gabapentin and Lamotrigine having the highest GP awareness rates. Almost 25% of GPs would initiate treatment following a first time seizure although only 30% would change therapy initiated by a consultant neurologist. Finally the majority of GPs were unhappy with the level of access to neurologists and 95% of GPs felt that the provision of an Epilepsy Clinical Nurse Specialist would help alleviate the problem.

Have the New GP Contract and NICE guidelines improved the clinical care of people with epilepsy?

PURPOSE: This retrospective audit was to assess the effect of the New General Practitioner (GP) Contract and National Institute for Health and Care Excellence (NICE) guidelines on the care and management of people with epilepsy (PWE) during the period of observation from April 2004 to April 2009. METHOD: The case notes of 540 people on anti-epilepsy drugs (AEDs) aged 16 years were reviewed in 13 general practices serving Ellesmere Port and Neston. RESULTS: Forty-nine percent of people with poorly controlled epilepsy were not under shared care. Diagnostic doubt existed in 25 (5%) people. There was no evidence that the original diagnosis had been actively reviewed by the GP in any case. There were 98 (18%) women of childbearing age, in 21 of whom there was no evidence of pre-conceptual counselling ever having taken place, and 61 (62%) were not receiving folic acid routinely. Thirty-nine (7%) people were demonstrably non-compliant, whilst 74 (14%) people had prescription anomalies consisting mainly of inappropriate multi-dose regimens. CONCLUSION: Despite marked improvements in review rates after the introduction of the New GP Contract five years previously, there are still significant unmet needs in this patient group. Clinical Commissioning Groups (CCGs) should consider funding an intermediate tier of care incorporating GPs with a special interest in epilepsy (GPwSIes) and Epilepsy Nurse Specialists (ENS) for PWE to improve and maintain existing and future primary care, as epilepsy is phased out of the Quality and Outcomes Framework (QOF).

Bone protection and anti-epileptic drugs: the effect of audit and computer messaging on supplementation prescribing practices.

OBJECTIVE: This audit assessed the impact of individualised written recommendations and a computer message, on repeat prescriptions for calcium and vitamin D supplements, for patients on long term AEDs. METHODS: 1041 adult patients with epilepsy were retrospectively followed from 2004, from the time of the introduction of the Quality and Outcomes Framework (QOF) and the publication of the National Institute of Clinical Evidence (NICE) guidelines for epilepsy, up until 2011. In 2009 a clinical notes review of 414 of the above patients, in Ellesmere Port and Neston (13 practices) was performed, suggesting supplementation, where appropriate, in a written report. A computer message was added to relevant prescriptions also recommending supplements, in the above practices plus all 26 practices in Chester and the surrounding area. The number of patients receiving repeat prescription for supplements in each area between 2004 and 2011 was analysed. RESULTS: There was a significant increase in the repeat prescriptions of supplements in 2010/11 after the interventions, the increase being most marked in Ellesmere Port and Neston where both written recommendations and computer message had occurred compared with the two areas with the computer message only. CONCLUSION: Quality audit with written recommendations, and a message added to the General Practice (GP) computer systems significantly increased the number of repeat prescriptions of calcium and vitamin D supplements in this group of patients. PRACTICE IMPLICATIONS: Where clear guidelines are established, this study demonstrates that continuing education and counselling of GPs and use of computer messaging would result in improved compliance with such guidelines.

Long-term risk of developing epilepsy after febrile seizures: a prospective cohort study.

OBJECTIVE: We report the prospective follow-up of a cohort of people from the onset of febrile seizures for a median of 24 years to estimate the long-term risk of developing epilepsy. METHODS: The National General Practice Study of Epilepsy is a large prospective community study of 1,195 people with a first suspected seizure followed from the 1980s, of whom 220 (18%) had febrile seizures. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) for subsequent epilepsy were calculated in 5-year age bands. RESULTS: Follow-up information was obtained for 181 (83%) people with a mean follow-up for the whole cohort of 21.6 (SD 6.0) years. Of these, 175 (97%) were seizure-free in the preceding 5 years, whereas 171 (94%) were seizure-free and off antiepileptic drugs. Six percent developed epilepsy, but the risk of developing epilepsy in the cohort over the whole follow-up period was almost 10 times that of the general population (SIR 9.7, 95% CI 5.7-16.4). The SIR was significantly elevated in the 0- to 14-year age groups but not in the 15- to 19-year age group (SIR 4.5, 95% CI 0.6-32.1). CONCLUSION: The risk of developing epilepsy in people who had febrile seizures seems to decrease with time. Further long-term studies are needed to confirm this.

Prognostic factors, morbidity and mortality in tonic-clonic status epilepticus: a review.

OBJECTIVES: to determine how the duration of SE, the EEG findings during/after SE, the depth of coma at presentation and age impact on the prognosis of convulsive status epilepticus indepedent of aetiology and to analyse the outcome of status epilepticus with respect to mortality and morbidity (the latter measured in terms of functional decline, cognitive/intellectual decline and the prospective risk of epilepsy). DESIGN: a systematic review of all studies of status epilepticus (SE) with greater then 30 patients published from the 01/01/1990 up until 31/12/2009. RESULTS: oveall the longer the duration of SE the worse the prognosis particularly after 1-2h of continuous seizures although this affect may be lost after 10h. The depth of coma correlates well with outcome. Only periodic epileptiform discharges (PEDs) have been shown to be associated with a poorer outcome in most (but not all) studies although this is probably related to the underlying aetiology. Age is an important prognostic factor with children having a better prognosis then adults. CONCLUSIONS: age and depth of coma at presentation appear to be the strongest predictors of outcome of SE independent of aetiology with the duration of SE and the EEG findings less important.

The uncommon causes of status epilepticus: a systematic review.

This paper reports the first systematic review of uncommon causes of status epilepticus reported in the literature between 1990 and 2008. Uncommon causes are defined as those not listed in the main epidemiological studies of status epilepticus. 181 causes were identified. These were easily categorised into 5 specific aetiological categories: immunological disorders, mitochondrial disorders, infectious diseases, genetic disorders and drugs/toxins. A sixth category of 'other causes' has also been included. Knowledge of these causes is important for clinical management and treatment, and also for a better understanding of the pathophysiology of status epilepticus.