Neuronal current imaging of epileptic activity: An MRI study in patients with a first unprovoked epileptic seizure.

OBJECTIVE: This study evaluates the performance of the novel MRI sequence stimulus-induced rotary saturation (SIRS) to map responses to interictal epileptic activity in the human cortex. Spin-lock pulses have been applied to indirectly detect neuronal activity through magnetic field perturbations. Following initial reports about the feasibility of the method in humans and animals with epilepsy, we aimed to investigate the diagnostic yield of spin-lock MR pulses in comparison with scalp-EEG in first seizure patients. METHODS: We employed a novel method for measurements of neuronal activity through the detection of a resonant oscillating field, stimulus-induced rotary saturation contrast (SIRS) at spin-lock frequencies of 120 and 240 Hz acquired at a single 3T MRI system. Within a prospective observational study, we conducted SIRS experiments in 55 patients within 7 days after a suspected first unprovoked epileptic seizure and 61 healthy control subjects. In this study, we report on the analysis of data from a single 3T MRI system, encompassing 35 first seizure patients and 31 controls. RESULTS: The SIRS method was applicable in all patients and healthy controls at frequencies of 120 and 240 Hz. We did not observe any significant age- or sex-related differences. Specificity of SIRS at 120 Hz was 90.3% and 93.5% at 240 Hz. Sensitivity was 17.1% at 120 Hz and 40.0% at 240 Hz. SIGNIFICANCE: SIRS targets neuronal oscillating magnetic fields in patients with epilepsy. The coupling of presaturated spins to epilepsy-related magnetic field perturbations may serve as a-at this stage experimental-diagnostic test in first seizure patients to complement EEG findings as a standard screening test. PLAIN LANGUAGE SUMMARY: Routine diagnostic tests carry several limitations when applied after a suspected first seizure. SIRS is a noninvasive MRI method to enable time-sensitive diagnosis of image correlates of epileptic activity with increased sensitivity compared to routine EEG.

Causes and prognosis of adults experiencing a first seizure in adulthood: A pilot cohort study conducted in five countries in Latin America.

There are limited data on first seizure (FS) among adults in low and middle-income countries. We describe findings from a prospective cohort study involving 180 adults presenting with seizures in emergency departments in five Latin American countries. Overall, 102 participants (56.7%) had acute symptomatic seizures (ASyS) while 78 (43.3%) had unprovoked seizures (UPS). Among patients with ASyS, 55 (53.9%) had structural causes, with stroke (n = 24, 23.5%), tumor (n = 10, 9.8%), and trauma (n = 3, 3%) being the most frequent. Nineteen patients (18.6%) had infectious causes, including four (4%) with meningoencephalitis, three (3%) neurocysticercosis, and two (2%) bacterial meningoencephalitis. Twenty patients (19.6%) had metabolic/toxic evidence, including four (4%) with uremic encephalopathy, two (2%) hyponatremia, and three (3%) acute alcohol intoxication. Immune dysfunction was present in seven (7%) patients and neurodegenerative in two (2%). Among participants with UPS, 45 (57.7%) had unknown etiology, 24 (30.7%) had evidence of structural disorders (remote symptomatic), four (5%) were related to infectious etiology (>7 days before the seizure), and five (6.4%) had genetic causes. During the 3- and 6-month follow-up, 29.8% and 14% of patients with UPS, respectively, experienced seizure recurrence, while 23.9% and 24.5% of patients with ASyS had seizure recurrence. Longer follow-up is necessary to assess seizure recurrence for patients with ASyS after the acute cause is resolved and to determine the 10-year risk of recurrence, which is part of the definition of epilepsy. PLAIN LANGUAGE SUMMARY: We monitored 180 adults who presented with their first seizure in emergency departments across five Latin American countries. Among these patients, 57% had acute symptomatic seizures, with structural causes such as stroke (23%), infection (17%), or tumor (10%) being more prevalent. Among the 43% with unprovoked seizures, 58% showed no identifiable acute cause, while 6.4% were due to genetics. Within 3 months after their initial seizure, 26.6% of individuals experienced a second seizure, with 11.9% continuing to have seizures in Months 3-6. Between Months 3 and 6, an additional 20% of patients encountered a second seizure. Research is needed to better understand the cause and prognosis of these patients to improve outcomes.

Guidelines and epilepsy practice: Antiseizure medication initiation following an unprovoked first seizure in adults.

OBJECTIVES: Adherence rate to evidence-based clinical practice guidelines is relatively low and the impact of guidelines on clinical practice in epilepsy is variable. The 2015 practice guideline on the management of an unprovoked first seizure in adults specifies clinical variables associated with increased risk of seizure recurrence and the impact of immediate antiseizure medication (ASM) treatment on seizure outcome. We aimed to evaluate the impact of the evidence-based guideline for the management of an unprovoked first seizure in adults on clinical practice in our adult neurology department. METHODS: We retrospectively reviewed the computerized database of 169 adult patients admitted to the adult neurology department at Shamir-Assaf Harofeh Medical Center following a first unprovoked seizure between October 2011 and October 2018. RESULTS: ASMs were initiated in 86% of patients with a first unprovoked seizure pre- and in all patients admitted post- guideline publication. Monotherapy and use of old generation ASMs were more common in both groups and a combination of old- and new generation ASMs - among the pre-guideline group. The pre-guideline decision to initiate ASM treatment was significantly influenced only by epileptiform discharges in the electroencephalogram (EEG). DISCUSSION: This is the first study to evaluate the impact of the 2015 practice guideline on the initiation of ASM treatment after a first unprovoked seizure in adults. Further studies are needed to assess the global contribution of the guideline to clinical practice and its impact on patient outcomes.

Antiseizure medication ≤48 hours portends better prognosis in new-onset epilepsy.

BACKGROUND: Several studies found that patients with new-onset epilepsy (NOE) have higher seizure recurrence rates if they presented already prior seizures. These observations suggest that timing of antiseizure medication (ASM) is crucial and should be offered immediately after the first seizure. Here, we wanted to assess whether immediate ASM is associated with improved outcome. METHODS: Single-center study of 1010 patients (≥16 years) who presented with a possible first seizure in the emergency department between 1 March 2010 and 1 March 2017. A comprehensive workup was launched upon arrival, including routine electroencephalography (EEG), brain computed tomography/magnetic resonance imaging, long-term overnight EEG and specialized consultations. We followed patients for 5 years comparing the relapse rate in patients treated within 48 h to those with treatment >48 h. RESULTS: A total of 487 patients were diagnosed with NOE. Of the 416 patients (162 female, age: 54.6 ± 21.1 years) for whom the treatment start could be retrieved, 80% (333/416) were treated within 48 h. The recurrence rate after immediate treatment (32%; 107/333) was significantly lower than in patients treated later (56.6%; 47/83; p < 0.001). For patients for whom a complete 5-year-follow-up was available (N = 297, 123 female), those treated ≤48 h (N = 228; 76.8%) had a significantly higher chance of remaining seizure-free compared with patients treated later (N = 69; 23.2%; p < 0.001). CONCLUSIONS: In this retrospective study, immediate ASM therapy (i.e., within 48 h) was associated with better prognosis up to 5 years after the index event. Prospective studies are required to determine the value of immediate workup and drug therapy in NOE patients.

Clinical characteristics and diagnoses of 1213 children referred to a first seizure clinic.

OBJECTIVE: New-onset seizure-like events (SLEs) are common in children, but differentiating between epilepsy and its mimics is challenging. This study provides an overview of the clinical characteristics, diagnoses, and corresponding etiologies of children evaluated at a first seizure clinic (FSC), which will be helpful for all physicians involved in the care of children with SLEs. METHODS: We included 1213 children who were referred to the FSC of a Dutch tertiary children's hospital over a 13-year period and described their clinical characteristics, first routine EEG recording results, and the distribution and specification of their eventual epilepsy and non-epilepsy diagnoses. The time interval to correct diagnosis and the diagnostic accuracy of the FSC were evaluated. RESULTS: "Epilepsy" was eventually diagnosed in 407 children (33.5%), "no epilepsy" in 737 (60.8%), and the diagnosis remained "unclear" in 69 (5.7%). Epileptiform abnormalities were seen in 60.9% of the EEG recordings in the "epilepsy" group, and in 5.7% and 11.6% of the "no epilepsy" and "unclear" group, respectively. Of all children with final "epilepsy" and "no epilepsy" diagnoses, 68.6% already received their diagnosis at FSC consultation, and 2.9% of the children were initially misdiagnosed. The mean time to final diagnosis was 2.0 months, and 91.3% of all children received their final diagnosis within 12 months after the FSC consultation. SIGNIFICANCE: We describe the largest pediatric FSC cohort to date, which can serve as a clinical frame of reference. The experience and expertise built at FSCs will improve and accelerate diagnosis in children with SLEs. PLAIN LANGUAGE SUMMARY: Many children experience events that resemble but not necessarily are seizures. Distinguishing between seizures and seizure mimics is important but challenging. Specialized first-seizure clinics can help with this. Here, we report data from 1213 children who were referred to the first seizure clinic of a Dutch children's hospital. One-third of them were diagnosed with epilepsy. In 68.8% of all children-with and without epilepsy-the diagnosis was made during the first consultation. Less than 3% were misdiagnosed. This study may help physicians in what to expect regarding the diagnoses in children who present with events that resemble seizures.

Video-EEG in the first 24 hours after the first unprovoked seizure in patients with normal neurological examination and head CT scan.

PURPOSE: to determine the yield of Video-Electroencephalogram (VEEG) in the first 24 h in patients with a first unprovoked seizure and normal neurological examination, laboratory findings, and cranial CT scans. METHODS: we analyzed retrospectively the yield of VEEG performed in these patients in the emergency department. All the patients were subsequently seen in the Epilepsy Clinic, and the epilepsy diagnosis was confirmed. RESULTS: we included 19 patients who met the inclusion criteria; all of them underwent VEEG with the 10-20 system within the first 24 h after the seizure. The duration of the recordings averaged at 108.53 min and may or may not have included intermittent photic stimulation and sleep recording; 74% of the recordings were abnormal, with 26% being normal. Among the abnormal cases, epileptogenic activity was found in 47% and seizures in 26% of the patients; because both findings could be present in the same VEEG, 63% of all the VEEG showed epileptogenic alterations or seizures. The VEEG anomalies were recorded before the 20th minute (standard VEEG duration) in 58% of patients who exhibited epileptogenic activity and/or seizures, and after the 20th minute in 42%. CONCLUSION: conducting approximately 100-minute VEEGs within the first 24 h after a first unprovoked seizure can enhance the diagnostic yield in patients with epilepsy. However, the study has the limitations of its sample size and retrospective nature.

Added value of advanced workup after the first seizure: A 7-year cohort study.

OBJECTIVE: This study was undertaken to establish whether advanced workup including long-term electroencephalography (LT-EEG) and brain magnetic resonance imaging (MRI) provides an additional yield for the diagnosis of new onset epilepsy (NOE) in patients presenting with a first seizure event (FSE). METHODS: In this population-based study, all adult (≥16 years) patients presenting with FSE in the emergency department (ED) between March 1, 2010 and March 1, 2017 were assessed. Patients with obvious nonepileptic or acute symptomatic seizures were excluded. Routine EEG, LT-EEG, brain computed tomography (CT), and brain MRI were performed as part of the initial workup. These examinations' sensitivity and specificity were calculated on the basis of the final diagnosis after 2 years, along with the added value of advanced workup (MRI and LT-EEG) over routine workup (routine EEG and CT). RESULTS: Of the 1010 patients presenting with FSE in the ED, a definite diagnosis of NOE was obtained for 501 patients (49.6%). Sensitivity of LT-EEG was higher than that of routine EEG (54.39% vs. 25.5%, p < .001). Similarly, sensitivity of MRI was higher than that of CT (67.98% vs. 54.72%, p = .009). Brain MRI showed epileptogenic lesions in an additional 32% compared to brain CT. If only MRI and LT-EEG were considered, five would have been incorrectly diagnosed as nonepileptic (5/100, 5%) compared to patients with routine EEG and MRI (25/100, 25%, p = .0001). In patients with all four examinations, advanced workup provided an overall additional yield of 50% compared to routine workup. SIGNIFICANCE: Our results demonstrate the remarkable added value of the advanced workup launched already in the ED for the diagnosis of NOE versus nonepileptic causes of seizure mimickers. Our findings suggest the benefit of first-seizure tracks or even units with overnight EEG, similar to stroke units, activated upon admission in the ED.

National audit of pathways in epileptic seizure referrals (NAPIER): A national, multicentre audit of first seizure clinics throughout the UK and Ireland.

BACKGROUND: Current guidelines set clinical standards for the management of suspected first seizures and epilepsy. We aimed to assess if these standards are being met across first seizure clinics nationally, to describe variations in care and identify opportunities for service delivery improvement. METHODS: Multicentre audit assessing the care of adults (≥16 years) referred to first seizure clinics from 31st December 2019 going backwards (30 consecutive patients per centre). Patients with pre-existing diagnosis of epilepsy were excluded. Anonymised referral, clinic, and follow-up data are reported with descriptive statistics. RESULTS: Data provided for 727 patients from 25 hospitals in the UK and Ireland (median age 41 years [IQR 26-59], 52% males). Median time to review was 48 days (IQR 26-86), with 13.8% (IQR 3.3%-24.0%) of patients assessed within 2 weeks. Seizure recurrence was seen in 12.7% (IQR 6.6%-17.4%) of patients awaiting first appointment. Documentation for witness accounts and driving advice was evident in 85.0% (IQR 74.0%-100%) and 79.7% (IQR 71.2%-96.4%) of first seizure/epilepsy patients, respectively. At first appointment, discussion of sudden unexpected death in epilepsy was documented in 30.1% (IQR 0%-42.5%) of patients diagnosed with epilepsy. In epilepsy patients, median time to MRI neuroimaging was 37 days [IQR 22-56] and EEG was 30 days [IQR 19-47]. 30.4% ([IQR 0%-59.5%]) of epilepsy patients were referred to epilepsy nurse specialists. CONCLUSIONS: There is variability nationally in the documented care of patients referred to first seizure clinics. Many patients are facing delays to assessment with epilepsy specialists with likely subsequent impact on further management.

First seizure from sleep: Clinical features and prognosis.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). SIGNIFICANCE: 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.

Risk of recurrence in patients with an unprovoked tonic-clonic seizure and generalized epileptiform discharges on EEG.

OBJECTIVE: The decision to initiate treatment in patients with a first unprovoked seizure remains controversial. Studies have reported a recurrence rate ranging from 21%-50%, but most have included patients with different etiologies, electroencephalography (EEG) findings, and seizure types. This study aimed to determine the risk of recurrence in patients with a first unprovoked generalized tonic-clonic (GTC) seizure with evidence of generalized spike-wave discharges (GSWDs) on EEG and compare the efficacy of antiseizure medications (ASMs) in preventing recurrence. METHODS: This prospective study included consecutive patients who presented with a single GTC seizure, evidence of GSWDs on EEG, and a follow-up period of at least 1 year. All patients underwent extensive evaluation, including a 3-hour sleep-deprived video-EEG recording and an epilepsy protocol brain magnetic resonance imaging (MRI). Treatment with ASMs was recommended for all patients. The decision regarding the specific ASM to be used was left to the treating physician's discretion. RESULTS: A total of 57 patients with a median age of 19 years were included. A total of 41 patients agreed to be started on an ASM while 16 declined. Seizure recurred in 6 of 41 patients (14.6%) in the treated group compared to 11 of 16 (68.8%) in the untreated group (p = .00006). Valproate was significantly more efficacious than levetiracetam or lamotrigine (p = .04). Of the 15 patients who discontinued ASM treatment after remaining seizure-free for an average of 30 months, 6 (40%) experienced a seizure recurrence. SIGNIFICANCE: Patients with a first unprovoked GTC seizure and evidence of GSWDs on EEG have a high risk of recurrence if left untreated. Valproate is the most efficacious ASM for preventing recurrence in this population. A sizeable proportion of patients can be successfully tapered off medication after a period of seizure freedom. This study provides valuable information for guiding treatment decisions in this patient population.

The impact of the time to last seizure before admission to the epilepsy monitoring unit (EMU) on epilepsy classifications.

INTRODUCTION AND BACKGROUND: The impact of the timing of the last seizure (TTLS) prior to admission to the epilepsy monitoring unit (EMU) on epilepsy classification is unclear for which we conducted this study. METHODS: We reviewed patients with epilepsy admitted to EMU between January 2021 and April 2022 and identified TTLS before EMU admission. We considered EMU yield as whether; it confirmed epilepsy classification, added new knowledge to the classification, or failed to classify epilepsy. RESULTS: We studied 156 patients. There were 72 (46%) men, with a mean age of 30. TTLS was divided according to a one- or three-month cutoff. We confirmed the pre-EMU epilepsy classification in 52 (33%) patients, learned new findings on epilepsy classification in 80 (51%) patients, and failed to classify epilepsy in 24 (15%) patients. Patients with "confirmed epilepsy classifications" reported seizures sooner to EMU admission than other groups (0.7 vs. 2.3 months, p-value = 0.02, 95% CI; -1.8, -1.3). Also, the odds of confirming epilepsy classification were more than two times in patients with TTLS within a month compared to those with TTLS of more than a month (OR = 2.4, p-value = 0.04, 95% CI; 1.1, 5.9). The odds were also higher when the 3-month TTLS cutoff was considered (OR = 6.2, p-value = 0.002, 95% CI; 1.6, 40.2). Confirming epilepsy classification was also associated with earlier seizures recorded at one- or three-month cutoff (OR = 2.1 and OR = 2.3, respectively, p-value = 0.05). We did not observe similar findings when we modified the classification or failed to reach a classification. CONCLUSIONS: The timing of the last seizure before EMU admission appeared to influence the yield of EMU and enhanced the confirmation of epilepsy classifications. Such findings can improve the utilization of EMU in the presurgical evaluation of patients with epilepsy.

Anxiety and depressive symptoms in adults with new-onset seizures: A scoping review.

OBJECTIVE: Anxiety and depression are common comorbidities in people living with epilepsy. Emerging research suggests that these conditions may even predate epilepsy onset. This review aimed to summarize the prevalence of clinically significant anxiety and depressive symptoms in people with first seizures and newly diagnosed epilepsy, as well as clinicodemographic factors associated with these symptoms. METHODS: A scoping literature review was performed. OVID Medline and Embase were searched from January 1, 2000, through May 1, 2022. Articles of interest were selected based on predetermined inclusion and exclusion criteria. RESULTS: From 1836 studies identified on screening, 16 met eligibility criteria and were included in the review. Clinically significant anxiety and depressive symptoms, as determined by validated cutoff scores for anxiety and depression screening instruments, were common in people with first seizures (range 13-28%) and newly diagnosed epilepsy (range 11-45%). They were associated with a range of clinicodemographic factors including past psychiatric history and trauma, personality traits, self-esteem, and stigma profiles. SIGNIFICANCE: There is substantial evidence that clinically significant anxiety and depressive symptoms are often present at the time and shortly following the first seizure or epilepsy diagnosis. Future research is needed to better understand the complex interactions between these common psychiatric comorbidities, new-onset seizure disorders, and certain clinicodemographic characteristics. This knowledge may inform targeted and holistic treatment approaches.

Mortality after a first-ever unprovoked seizure.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. SIGNIFICANCE: 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.

Clinically important intracranial abnormalities in children presenting with first focal seizure.

BACKGROUND: Management of pediatric patients presenting with first seizure is challenging, especially with regards to emergent neuroimaging. The rate of abnormal neuroimaging findings is known to be higher in focal seizures than in generalized seizures, but those intracranial abnormalities are not always clinically emergent. In this study, we aimed to determine the rate and indicators for clinically important intracranial abnormalities that change acute management in children presenting with a first focal seizure to the pediatric emergency department (PED). METHODS: This study was conducted retrospectively in the PED at a University Children`s Hospital setting. The study population consisted of patients aged between 30 days and 18 years with first focal seizure and who had emergent neuroimaging at the PED between the years 2001 and 2012. RESULTS: There were 65 eligible patients meeting the study criteria. Clinically important intracranial abnormalities requiring emergent neurosurgical or medical intervention were detected in 18 patients (27.7%) at the PED. Four patients (6.1%) underwent emergent surgical procedures. Seizure recurrence and the need for acute seizure treatment in the PED were significantly associated with clinically important intracranial abnormalities. CONCLUSIONS: Neuroimaging study yielding of 27.7% shows that first focal seizure must be evaluated meticulously. From the emergency department`s point of view; we suggest that first focal seizures in children should be evaluated with emergent neuroimaging, if possible with magnetic resonance imaging. Especially patients with recurrent seizures at presentation requires more careful evaluation.

Operational diagnosis of epilepsy in children at undetermined risk: A meta-analysis of prognostic factors for seizure recurrence.

PURPOSE: According to the operational epilepsy definition adopted by the International League Against Epilepsy (ILAE) in 2014, in patients with one unprovoked seizure, clinicians must stratify the recurrence risk to determine if the criteria for diagnosis of epilepsy have been met and if antiseizure medications (ASM) are required. A remote symptomatic etiology was considered to be one of the best predictors for seizure recurrence, also according to the available prediction tools, but in children with a previously negative history and a normal neurological examination, estimating the probability of seizure relapse remains less obvious. This meta-analysis aimed to fill this gap of knowledge. METHODS: The PubMed, Embase, and Scopus databases were searched from January 2000 to December 2020. We selected studies reporting children (1 month-18 years old) presenting a first unprovoked seizure. The absence of a known remote neurological pathology had to be clearly stated in the paper or the idiopathic/cryptogenic group data were used; the finding of epileptogenic structural brain MRI abnormalities during the diagnostic workup at the moment of the first unprovoked seizure was not an exclusion criterion. Factors analyzed, as possible predictors of recurrence, included: age at onset, sex, family history of epilepsy, type of seizure (focal or generalized), epileptiform abnormalities on EEG, and epileptogenic structural brain MRI abnormalities. RESULTS: Four studies met the inclusion criteria and the sample size consisted of 741 children. The estimated recurrence rate within 3 years was 50% (95%CI:33.9%-66.0%). Among the predictors of recurrence, focal seizure (OR = 1.52; 95%CI = 1.05-2.19), epileptiform abnormalities on EEG (OR = 1.97; 95%CI = 1.31-2.96), and positive family history for epilepsy (OR = 2.37; 95%CI = 1.56-3.59) were associated with a statistically significant increased risk. CONCLUSION: The analysis of data available until now cannot adequately assess the risk of recurrence after a first unprovoked seizure in neurotypical children. Prospective and multicenter cohort studies are expected.

Paroxysmal slow wave events predict epilepsy following a first seizure.

OBJECTIVE: Management of a patient presenting with a first seizure depends on the risk of additional seizures. In clinical practice, the recurrence risk is estimated by the treating physician using the neurological examination, brain imaging, a thorough history for risk factors, and routine scalp electroencephalogram (EEG) to detect abnormal epileptiform activity. The decision to use antiseizure medication can be challenging when objective findings are missing. There is a need for new biomarkers to better diagnose epilepsy following a first seizure. Recently, an EEG-based novel analytical method was reported to detect paroxysmal slowing in the cortical network of patients with epilepsy. The aim of our study is to test this method's sensitivity and specificity to predict epilepsy following a first seizure. METHODS: We analyzed interictal EEGs of 70 patients admitted to the emergency department of a tertiary referral center after a first seizure. Clinical data from a follow-up period of at least 18 months were available. EEGs of 30 healthy controls were also analyzed and included. For each EEG, we applied an automated algorithm to detect paroxysmal slow wave events (PSWEs). RESULTS: Of patients presenting with a first seizure, 40% had at least one additional recurring seizure and were diagnosed with epilepsy. Sixty percent did not report additional seizures. A significantly higher occurrence of PSWEs was detected in the first interictal EEG test of those patients who were eventually diagnosed with epilepsy. Conducting the EEG test within 72 h after the first seizure significantly increased the likelihood of detecting PSWEs and the predictive value for epilepsy up to 82%. SIGNIFICANCE: The quantification of PSWEs by an automated algorithm can predict epilepsy and help the neurologist in evaluating a patient with a first seizure.

Governance of the clinical pathway and management of the patient suffering from epilepsy and drug-resistant epilepsy.

Epilepsy is a diffuse chronic neurological disease affecting around 50 million people worldwide. The diagnostic criteria by the International League against Epilepsy must be fulfilled to diagnose the disease, which is characterized by brief and transient episodes of abnormal neuronal activity involving one or both hemispheres, depending on the epilepsy type. The diagnosis of epilepsy should be properly and timely made because patients suffering from the disease are affected not only by seizure recurrence but also by epilepsy-related psychiatric and/or cognitive comorbidities that may have a huge impact with severe professional and social implications. It is of vital importance to define a specific governance model that has to be virtuously applied into the different phases of the clinical pathway of the patients with epilepsy in order to guarantee them the best model of care possible.

Perception of memory performance after first seizure in patients with and without an epilepsy diagnosis.

OBJECTIVES: Memory complaints in patients with epilepsy have been well-studied. Although memory complaints are commonly reported by patients with chronic epilepsy, to date, few studies exist on memory complaints at the onset of epilepsy. The present study investigated the presence of memory complaints and their relation to mood and memory performance in patients after their first seizure. Thereby, we examined differences between individuals who received a diagnosis of epilepsy immediately with the occurrence of their first seizure and those who were diagnosed as having the first epileptic seizure, without fulfilling the ILAE criteria for the diagnosis of epilepsy. METHODS: Sixty-one patients participated in the study and completed, among others, a memory task and questionnaires on memory complaints and depression after their first epileptic seizure. We investigated the level of memory complaints and their correlation and accuracy in classification with a memory measure. We compared patients who received an epilepsy diagnosis after the first seizure with those who did not. RESULTS: Memory complaints did not correlate with objective memory performance. Classification into impaired/unimpaired showed low concordance between memory complaints and neuropsychological memory measures. After their first epileptic seizure, patients reported few memory complaints overall (10%), and there were no differences in memory complaints between patients with and without an epilepsy diagnosis. CONCLUSION: At epilepsy onset, in contrast to established epilepsies, memory complaints are rare. Although influences of anticonvulsant drugs and seizures are not present at the beginning of epilepsy, this substantial absence of memory complaints at epilepsy onset emphasizes the need for comprehensive neurological and psychological treatment early with the given diagnosis. Treatment should focus on anticonvulsant drug regimens, patients' concerns and convey realistic expectations.

Anxiety of families after first unprovoked or first febrile seizure - A prospective, randomized pilot study.

OBJECTIVES: Parents of children with a first unprovoked seizure report high levels of stress and anxiety. Little is known however about interventions that might help to reduce anxiety. We aimed to evaluate anxiety of parents and children after a first unprovoked seizure and assess the anxiety-reducing effect of a semi-structured follow-up in a first seizure clinic (FSC). In comparison, parents of children with febrile seizures are also evaluated, as an example of anxiety evolution without follow-up intervention after provoked seizures. STUDY DESIGN: In this prospective, interventional study, patients presenting with a first unprovoked seizure were randomized to early care (EC) with follow-up in FSC within 3 weeks and late care (LC), follow-up in FSC after 4 months. Anxiety levels of parents and patients were scored with the State Trait Anxiety Inventory (STAI) after the initial seizure (T0), 3 and 12 months (T1, T2). To assess the effect of the semi-structured follow-up, anxiety scores were compared between the two groups at baseline, at T1 (i.e., after intervention in EC but prior to intervention in LC) and at T2. Parents of children with febrile seizures (FS) were prospectively followed up without intervention. RESULTS: Fifty two patients were included (EC n = 18, LC n = 18, FS n = 15). Initial state anxiety in parents was high in all groups. At T1 (i. e. after intervention in EC but not LC) state anxiety was significantly higher in LC (52.2 (16.7) vs. 33.3 (5.3), p < 0.01). This effect persisted after 12 months, despite intervention in LC in the meantime (39.0 (11.7) vs. 28.8 (6.2); p < 0.01)). The effect in children was similar (T1: 40.6 (8.3) vs. 29.8 (5.1); p < 0.05 and T2: 33.5 (4.7) vs. 24.7 (3.6); p < 0.01). State anxiety in FS decreased within 3 months without intervention (50.0 (14.5) to 33.7 (9.2)). CONCLUSIONS: A timely and structured follow-up in a FSC offers effective and sustained reduction of anxiety-levels after first unprovoked seizure in children. In contrast, anxiety after a first febrile seizure decreases over time without additional intervention.

Toward individualized prediction of seizure recurrence: Hippocampal neuroimaging features in a cohort of patients from a first seizure clinic.

PURPOSE: We performed an exploratory analysis of electroencephalography (EEG) and neuroimaging data from a cohort of 51 patients with first seizure (FS) and new-onset epilepsy (NOE) to identify variables, or combinations of variables, that might discriminate between clinical trajectories over a one-year period and yield potential biomarkers of epileptogenesis. METHODS: Patients underwent EEG, hippocampal and whole brain structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) within six weeks of the index seizure, and repeat neuroimaging one year later. We classified patients with FS as having had a single seizure (FS-SS) or having converted to epilepsy (FS-CON) after one year and performed logistic regression to identify combinations of variables that might discriminate between FS-SS and FS-CON, and between FS-SS and the combined group FS-CON + NOE. We performed paired t-tests to assess changes in quantitative variables over time. RESULTS: Several combinations of variables derived from hippocampal structural MRI, DTI, and MRS provided excellent discrimination between FS-SS and FS-CON in our sample, with areas under the receiver operating curve (AUROC) ranging from 0.924 to 1. They also provided excellent discrimination between FS-SS and the combined group FS-CON + NOE in our sample, with AUROC ranging from 0.902 to 1. After one year, hippocampal fractional anisotropy (FA) increased bilaterally, hippocampal radial diffusivity (RD) decreased on the side with the larger initial measurement, and whole brain axial diffusivity (AD) increased in patients with FS-SS; hippocampal volume decreased on the side with the larger initial measurement, hippocampal FA increased bilaterally, hippocampal RD decreased bilaterally and whole brain AD, FA and mean diffusivity increased in the combined group FS-CON + NOE (corrected threshold for significance, q = 0.017). CONCLUSION: We propose a prospective, multicenter study to develop and test models for the prediction of seizure recurrence in patients after a first seizure, based on hippocampal neuroimaging. Further longitudinal neuroimaging studies in patients with a first seizure and new-onset epilepsy may provide clues to the microstructural changes occurring at the earliest stages of epilepsy and yield biomarkers of epileptogenesis.