First-ever Unprovoked Seizure Research Articles

First-ever seizure and eligibility for commercial motor vehicle driving

BackgroundAfter a first-ever seizure, 6 months of seizure freedom is usually required before returning to driving a private motor vehicle, after which the annual risk of seizure recurrence has fallen...

First seizure from sleep: Clinical features and prognosis.

Patients with a first-ever unprovoked seizure commonly have subsequent seizures and identifying predictors of recurrence has important management implications. Both prior brain insult and epileptiform abnormalities on electroencephalography (EEG) are established predictors of seizure recurrence. Some studies suggest that a first-ever seizure from sleep has a higher likelihood of recurrence. However, with relatively small numbers and inconsistent definitions, more data are required. Prospective cohort study of adults with first-ever unprovoked seizure seen by a hospital-based first seizure service between 2000 and 2015. Clinical features and outcomes of first-ever seizure from sleep and while awake were compared. First-ever unprovoked seizure occurred during sleep in 298 of 1312 patients (23%), in whom the 1-year cumulative risk of recurrence was 56.9% (95% confidence interval [CI] 51.3-62.6) compared to 44.2% (95% CI 41.1-47.3, p < .0001) for patients with first-ever seizure while awake. First-ever seizure from sleep was an independent predictor of seizure recurrence, with a hazard ratio [HR] of 1.44 (95% CI 1.23-1.69), similar to epileptiform abnormalities on EEG (HR 1.48, 95% CI 1.24-1.76) and remote symptomatic etiology (HR 1.47, 95% CI 1.27-1.71). HR for recurrence in patients without either epileptiform abnormalities or remote symptomatic etiology was 1.97 (95% CI 1.60-2.44) for a sleep seizure compared to an awake seizure. For first seizure from sleep, 76% of second seizures also arose from sleep (p < .0001), with 65% of third seizures (p < .0001) also from sleep. Seizures from sleep were less likely to be associated with injury other than orolingual trauma, both with the presenting seizure (9.4% vs 30.6%, p < .0001) and first recurrence (7.5% vs 16.3%, p = .001). First-ever unprovoked seizures from sleep are more likely to recur, independent of other risk factors, with recurrences also usually from sleep, and with a lower risk of seizure-related injury. These findings may inform treatment decisions and counseling after first-ever seizure.

Mortality after a first-ever unprovoked seizure.

Although increased mortality associated with epilepsy is well understood, data in patients after their first-ever seizure are limited. We aimed to assess mortality after a first-ever unprovoked seizure and identify causes of death (CODs) and risk factors. A prospective cohort study was undertaken of patients with first-ever unprovoked seizure between 1999 and 2015 in Western Australia. Two age-, gender-, and calendar year-matched local controls were obtained for each patient. Mortality data, including COD, based on International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes, were obtained. Final analysis was performed in January 2022. One thousand two hundred seventy-eight patients with a first-ever unprovoked seizure were compared to 2556 controls. Mean follow-up was 7.3 years (range = .1-20). Overall hazard ratio (HR) for death after a first unprovoked seizure compared to controls was 3.06 (95% confidence interval [CI] = 2.48-3.79), with HRs of 3.30 (95% CI=2.26-4.82) for those without seizure recurrence and 3.21 (95% CI=2.47-4.16) after a second seizure. Mortality was also increased in patients with normal imaging and no identified cause (HR=2.50, 95% CI=1.82-3.42). Multivariate predictors of mortality were increasing age, remote symptomatic causes, first seizure presentation with seizure cluster or status epilepticus, neurological disability, and antidepressant use at time of first seizure. Seizure recurrence did not influence mortality rate. The commonest CODs were neurological, most relating to the underlying cause of seizures rather than being seizure-related. Substance overdoses and suicide were more frequent CODs in patients compared to controls and were commoner than seizure-related deaths. Mortality is increased two- to threefold after a first-ever unprovoked seizure, independent of seizure recurrence, and is not only attributable to the underlying neurological etiology. The greater likelihood of deaths related to substance overdose and suicide highlights the importance of assessing psychiatric comorbidity and substance use in patients with first-ever unprovoked seizure.

Filamin A Variant as a Possible Second-Hit Gene Promoting Moyamoya Disease-like Vascular Formation Associated With RNF213 p.R4810K Variant.

Background and ObjectiveThe objective of this case report was to identify a second-hit gene that may promote Moyamoya disease (MMD)–like vascular formation in an individual having the RNF213 p.R4810K variant.MethodsWe performed magnetic resonance imaging and genetic analyses of RNF213 and FLNA in a 21-year-old woman, who showed Ehlers-Danlos–like symptoms and developed a first-ever unprovoked seizure, and of her healthy parents.ResultsWe identified bilateral periventricular nodular heterotopia (PNH) as the cause of seizures and MMD-like vascular formation in the patient. The patient had the RNF213 p.R4810K variant. Exome analysis identified c.4868delG in the X-linked FLNA gene encoding filamin A p.G1623V fs*41, which could explain PNH and Ehlers-Danlos–like symptoms. Her mother had the same FLNA variant and had asymptomatic bilateral PNH, whereas her father had the RNF213 variant and had normal cerebrovascular structure.DiscussionThe family study suggested that the FLNA variant promoted MMD-like vascular formation in a patient having the RNF213 variant, while the RNF213 variant amplified the phenotypic changes elicited by the FLNA abnormality. Collectively, we identified a gene abnormality in filamin A, a target of RNF213-mediated proteasomal degradation, that may promote MMD-like vascular formation as a possible second-hit gene in individuals having the RNF213 p.R4810K variant.

Revisiting an ancient legend: influence of the lunar cycle on occurrence of first-ever unprovoked seizures.

The mythical effect of the lunar cycle on seizures has been debated over time. Previously healthy individuals presenting with first-ever seizures in whom investigations are negative often invoke questions about potential reasons including a full moon. To determine whether there is a temporal relationship between the occurrence of the first-ever unprovoked seizure and the lunar cycle. We studied adults who presented with a first-ever unprovoked seizure to two tertiary centres in Australia. Seizure onset time was obtained from the emergency department and ambulance documentations. We used Poisson regression modelling and incidence rate ratios (IRR) to determine whether seizures have a preponderance for a particular lunar phase. We performed further analysis on 'first seizure epilepsy' and 'first seizure not epilepsy' subgroups based on the International League Against Epilepsy criteria for a diagnosis of epilepsy after a single unprovoked seizure. We analysed 1710 patients (38% females; median age 39 years), of whom 18% had epileptiform abnormalities on electroencephalogram (EEG) and potentially epileptogenic lesions were detected on neuroimaging in 28%. Based on the EEG and imaging findings, 684 (40%) patients were categorised as 'first seizure epilepsy' and 1026 (60%) 'first seizure not epilepsy'. The whole cohort and subgroup analysis demonstrated no significant difference in the seizure occurrence among the four lunar quarters. First unprovoked seizures are not influenced by the lunar cycle. Patients pondering the cause of their first-ever unprovoked seizure can be reassured that the full moon was not responsible.

Identification and Characterization of Pure Sleep Epilepsy in a Cohort of Patients With a First Seizure.

Our aim was to study the development of pure sleep epilepsy after a first-ever seizure from sleep in adults. This was a prospective observational study of patients seen at a tertiary hospital-based first seizure clinic between 2000 and 2011. Adults with a first-ever unprovoked seizure from sleep were consecutively recruited. All patients were followed up at least once after the initial seizure, and those not requiring regular clinical review were contacted every 1 to 2 years. The timing and pattern of subsequent seizures and potential predictors of future awake seizures were analyzed. Two hundred thirty-nine adults with a first-ever unprovoked seizure from sleep were identified. Sixty-one percent were male; mean age was 43 years (range 14-88 years); and median follow-up of 8.8 years (range 2 months-18 years). Of the 174 patients who had recurrent seizures, 130 patients (75%) had their second seizure from sleep, and of these, 76 of 94 (81%) also had their third seizure from sleep. Eighty-nine patients (37%) developed awake seizures during follow-up. In half of these patients, the awake seizure occurred within 2 years of the initial seizure. The risk of an awake seizure within 1 year of a first-ever seizure from sleep was 13.9% (95% CI 9.4%-18.3%), falling to 2.0% to 5.3% per year after 3 years. The risks of an awake seizure within 1 year of a second or third consecutive sleep seizure were 9.9% (95% CI 4.6%-15.3%) and 8.7% (95% CI 2.0%-15.4%), respectively, and similarly decreased with time. Most initial seizure recurrences after a first-ever sleep seizure occur during sleep. While more than one-third eventually had awake seizures, the annual risk of an awake seizure was ≤14% and decreased with time, albeit with a small ongoing risk of between 2% and 5% per year. These findings may be used in counseling patients with seizures from sleep and to inform driving recommendations.

Temporal patterns in the first unprovoked seizure

ObjectiveCyclic phenomena in epilepsy are well recognized. We investigated a multicenter cohort of unprovoked first seizure presentations to determine whether seizures have a preponderance to occur in: a particular time of the day, a particular day of the week, a particular month of the year, day time versus night time, and wakefulness versus sleep. MethodsWe retrospectively studied adults who presented with a first-ever unprovoked seizure to the First Seizure Clinic at two tertiary centers in Australia. Seizure onset time was obtained from the emergency department and ambulance documentations. Electro-clinical and neuroimaging findings were reviewed. We used histograms and Poisson regression modeling to determine whether seizures have a preponderance to occur at a particular time and calculated incidence rate ratios (IRR). We performed further analysis on patients with “first seizure epilepsy” and “first seizure not epilepsy” based on the ILAE criteria for a diagnosis of epilepsy after a single unprovoked seizure, as well as comparing patients that could be categorized as having a generalized-onset seizure versus those with focal–onset seizures. ResultsWe analyzed 1724 patients (38% females; age range 14–97 yr, median 39 yr), of whom 18% had epileptiform abnormalities on EEG and potentially epileptogenic lesions were detected on neuroimaging in 28%. Whole cohort analysis shows the incidence rate ratios (IRR) of seizures varied significantly across the 24-hour clock-time of the day (p < 0.001), peaking at hour 12 (IRR 3.18). The first unprovoked seizure was significantly less likely to be reported during the night (IRR 0.61, p < 0.001) and during sleep (IRR 0.29, p < 0.001). Both the “first seizure epilepsy” and “first seizure not epilepsy” subgroups’ analysis demonstrated similar patterns. An infraradian pattern was also noted with seizures most likely to occur in May (IRR 1.29, p = 0.02). Both “first seizure epilepsy – generalized” and “first seizure epilepsy – focal” groups had a preponderance for seizures to occur during the day versus night and wakefulness as opposed to sleep, but the association was more robust for generalized seizures. ConclusionsOur results suggest that temporal patterns are seen in patients with first-ever unprovoked seizures, including those that meet contemporary criteria for epilepsy. These results raise the possibility that first unprovoked seizures have intrinsic rhythmicity similar to epileptic seizures.

Immediate vs delayed treatment of first unprovoked seizure

Deciding whether to treat or not to treat a first-ever seizure can be difficult, particularly when additional history provides no clear provoking mechanism and the critical ancillary tests such as MRI and EEG are uninformative. The practical clinical definition of epilepsy presented in the widely acknowledged International League Against Epilepsy (ILAE) official report is met under the following conditions: 2 unprovoked seizures >24 hours apart, 1 unprovoked seizure and seizure recurrence probability of >60% over the next 10 years, or diagnosis of an epilepsy syndrome.1 The report explicitly states that treatment decisions are distinct from diagnosis (i.e., the presence of disease does not necessitate treatment and the absence of disease does not preclude treatment) and that treatment decisions should be tailored to the clinical scenario and individual patient. Despite this caveat, in practice, treatment decisions are frequently based on the ILAE's 60% threshold, resulting, for example, in deferred treatment in patients with first-ever unprovoked seizure and apparent probability of recurrence <60%, particularly in light of potential antiepileptic drug (AED) adverse side effects and no known disease-modifying properties of AEDs.2 Because the reported seizure recurrence rates in patients with a first unprovoked seizure have ranged between 21% and 45% in the first 2 years,3 the practical result is that patients presenting with unprovoked first seizure and unrevealing workup are, almost by default, not treated with an AED.4,5

The predictive value of electroencephalography in recurrence of the first-ever unprovoked idiopathic seizure

Aim of the study We aimed to study the role of electroencephalography (EEG) and its predictive value for recurrence after the first-ever seizure. Patients and methods Patients who presented with first idiopathic seizure attack were included in this prospective study. The study group included 70 patients (39 male and 31 female). Their ages ranged from 1 to 58 years. All patients included were subjected to history taking and full analysis of the seizure, full neurological examination, routine laboratory tests, neuroimaging, and EEG evaluation, and then all patients were interviewed monthly for 3 successive months. Results Sixteen patients (23%) had focal seizures and 54 patients (77%) had generalized seizure. Nocturnal seizures were found in 45.7% of patients, whereas diurnal seizures were found in 54.3% patients. Aura was recorded in 17% of cases, whereas postictal state (confusion, headache, muscle ache, and Todd’s paralysis) occurred in 60% of cases. Past history of febrile seizures was present in 17% of cases, family history of epilepsy was positive in 10% of cases, and 31.4% of cases had positive consanguinity. Abnormal EEG was found in 54.3% of patients [31.4% of patients had generalized epileptiform discharge, 15.7% of patients had focal epileptiform discharge with or without secondary generalization, and 7.2% of patients had no specific changes (focal or generalized slowness)] and lastly normal EEG was found in 45.7% of patients. After 3 months of follow-up, 37 patients (52.9%) had recurrence of seizure: 75.6% of patients had generalized seizures and 24.4% of patients had focal seizures. The percent of recurrence among patients with abnormal EEG was 70.3% and that among those with normal EEG was 29.7%. As regards EEG findings, there were a significant correlation between abnormal EEG and generalized epileptiform discharge and recurrence of seizure. Conclusion EEG, especially during the first 48 h after seizure, had a prognostic value for recurrence of seizure.

Is the first seizure epilepsy--and when?

Epilepsy has recently been redefined to include a single unprovoked seizure if the probability of recurrence is ≥60% over the following 10 years. This definition is based on the estimated risk of a third seizure after two unprovoked seizures, using the lower-limit 95% confidence interval (CI) at 4 years, and does not account for the initially high recurrence rate after first-ever seizure that rapidly falls with increasing duration of seizure freedom. We analyzed long-term outcomes after the first-ever seizure, and the influence of duration of seizure freedom on the likelihood of seizure recurrence, and their relevance to the new definition of epilepsy. Prospective analysis of 798 adults with a first-ever unprovoked seizure seen at a hospital-based first seizure clinic between 2000 and 2011. The likelihood of seizure recurrence was analyzed according to the duration of seizure freedom, etiology, electroencephalography (EEG), and neuroimaging findings. The likelihood of seizure recurrence at 10 years was ≥60% in patients with epileptiform abnormalities on EEG or neuroimaging abnormalities, therefore, meeting the new definition of epilepsy. However, the risk of recurrence was highly time dependent; after a brief period (≤12 weeks) of seizure freedom, no patient group continued to fulfill the new definition of epilepsy. Of 407 patients who had a second seizure, the likelihood of a third seizure at 4 years was 68% (95% CI 63-73%) and at 10 years was 85% (95% CI 79-91%). The duration of seizure freedom following first-ever seizure substantially influences the risk of recurrence, with none of our patients fulfilling the new definition of epilepsy after a short period of seizure freedom. When a threshold was applied based on the 10-year risk of a third seizure from our data, no first-seizure patient group ever had epilepsy. These data may be utilized in a definition of epilepsy after a first-ever seizure.

Are seizures in the setting of sleep deprivation provoked?

It is generally accepted that sleep deprivation contributes to seizures. However, it is unclear whether a seizure occurring in the setting of sleep deprivation should be considered as provoked or not and whether this is influenced by seizure type and etiology. This information may have an important impact on epilepsy diagnosis and management. We prospectively analyzed the influence of sleep deprivation on the risk of seizure recurrence in patients with first-ever unprovoked seizures and compared the findings with patients with first-ever provoked seizures. Of 1026 patients with first-ever unprovoked seizures, 204 (20%) were associated with sleep deprivation. While the overall likelihood of seizure recurrence was slightly lower in sleep-deprived patients with first-ever seizures (log-rank p=0.03), sleep deprivation was not an independent predictor of seizure recurrence on multivariate analysis. Seizure recurrence following a first-ever unprovoked seizure associated with sleep deprivation was far more likely than for 174 patients with a provoked first-ever seizure (log-rank p<0.0001). Our findings support the International League Against Epilepsy recommendation that seizures occurring in the setting of sleep deprivation should not be regarded as provoked.

First seizure in the older patient: Clinical features and prognosis

The prognosis of first seizure in the elderly has rarely been studied. Despite this, anti-epileptic drug treatment following first seizure is often recommended in older adults due to the perception that recurrence is inevitable and associated with significant morbidity. This study aims to establish whether older patients presenting with first-ever seizure are more likely to have a second seizure or not, and to examine their clinical features including seizure-related morbidity. Prospective observational study of adults seen by a hospital-based first seizure service between 2000 and 2011. The prognosis and clinical features of older (aged ≥65 years) and younger (aged 16-64 years) patients were compared. 139 of 1008 patients with first-ever unprovoked seizure were aged ≥65 years (mean age 74 years). The majority of these older patients were healthy (95% ambulant, 81% Rankin score ≤2). The likelihood of a second seizure at one year was 53% (95% CI 45-62) in older patients and 48% (95% CI 44-51) in younger patients. Independent predictors of seizure recurrence were remote symptomatic etiology, first seizure arising from sleep, epileptiform abnormality on EEG and partial seizures but not age. Older patients were less likely to suffer a seizure-related injury with both the presenting seizure and the first recurrence. With first-ever seizure age is not an independent predictor of seizure recurrence and older patients are less likely to sustain a seizure-related injury. Treatment decisions in older patients presenting with first-ever seizure should be based on established risk factors for seizure recurrence rather than age.

Neuroimaging of first-ever seizure: Contribution of MRI if CT is normal.

The role of neuroimaging in the assessment of a first-ever seizure has not been well-defined, in particular the utility of MRI when CT is normal. The results of neuroimaging (CT brain, MRI brain, or both) in 1,013 adults with first-ever unprovoked seizure were correlated with clinical features and seizure outcome. Epileptogenic lesions were identified in 29%. Of patients with a normal CT who also had MRI, 12% had an epileptogenic lesion on MRI, the strongest independent predictor of which was a focal abnormality on EEG. Patients with an epileptogenic lesion had a higher risk of seizure recurrence, including when this was only evident on MRI.

PATH38 When is it safe to return to driving after a first-ever seizure?

IntroductionThe risk of recurrence following first-ever seizure is about 50% warranting driving restriction during the period of highest risk. In the UK, the duration of nondriving following a first unprovoked...

The diagnostic aid of routine EEG findings in patients presenting with a presumed first-ever unprovoked seizure

Data are available on the yield of a single EEG recording in patients with epilepsy but there is little information on EEG findings as an aid in supporting the diagnosis of an epileptic event in patients presenting with a first-ever event suspected of being an unprovoked seizure. We retrieved files of patients above the age of 15 years admitted through the emergency room during 1991–1995 with presumed first-ever unprovoked seizure. There were 91 patients (age 50±24; 52 males), of whom 66% had a presumed seizure of unknown origin and 34% had presumed remote symptomatic seizures. About 80% had generalized seizures (primarily or secondarily). In all the patients an EEG had been performed within 48 h of the event. Abnormal EEGs were obtained in 69%, with epileptiform activity in 21% (10% focal, 9% generalized and 2% focal and generalized), slowing in 58% (21% focal, 31% generalized and 7% focal and generalized), and both epileptiform activity and slowing in 10%. Epileptiform activity was most common in younger patients with seizures of unknown origin, compared with older individuals with symptomatic seizures (34, 38 vs. 27%, 7%, P=0.001). We conclude that following a single unprovoked presumed seizure, adults commonly exhibit abnormalities in an EEG recorded close in time to the event. The EEG is particularly helpful in supporting the epileptic nature of the event in younger patients and in those with seizures of unknown origin.