Dose Monitoring of Lamotrigine Monotherapy in Pregnancy: Are Pregnant Women with Epilepsy Currently Optimally Managed? A Systematic Review.

BACKGROUND: Lamotrigine monotherapy is the first-line treatment for epilepsy in pregnant women. However, altered pharmacokinetics during pregnancy can lead to suboptimal drug levels and increased seizure risk. This systematic review aimed to evaluate current therapeutic drug monitoring (TDM) strategies for lamotrigine monotherapy in pregnant women with epilepsy and provide guidance for monitoring and dose adjustments. METHODS: A systematic search was performed using the Ovid-MEDLINE, Ovid-EMBASE, and Ovid-Cochrane Central Register of Controlled Trials databases. Studies were included if data on lamotrigine dosing, concentration, TDM strategies, efficacy, or safety were available. RESULTS: Eleven studies were analyzed, revealing heterogeneity in outcomes with selective reporting of TDM strategies; however, clear similarities were observed. Blood samples were collected every 1-3 months during pregnancy to maintain prepregnancy baseline drug levels. Lamotrigine's apparent and relative clearance increased across trimesters, particularly in the second and third trimesters, coinciding with a period of increased seizure frequency and required dose adjustments. Details on dose adjustments were limited. Some studies have proposed using the threshold of the ratio to the target concentration to predict increased seizure risk. No distinct association was observed between adverse newborn outcomes and lamotrigine dose or serum concentration. Few maternal adverse effects have been reported after delivery, confirming the necessity of empirical postpartum tapering. CONCLUSIONS: Further studies are required to establish evidence-based standardized protocols encompassing all aspects of TDM. Early interventions, such as empirical dose increases during pregnancy and postpartum tapering, and routine monitoring from preconception to the postpartum period may enhance seizure control, reducing the risk of breakthrough seizures for the mother and unborn child.

Successful stereoelectroencephalography re-evaluation in epilepsy patients after failed initial subdural grid evaluation.

OBJECTIVE: Epilepsy surgery success is dependent on accurate localization of the epileptogenic zone. Despite the use of invasive EEG using subdural grids and strips, surgical failures can occur. In this series, we explore the utility of a second evaluation with stereoelectroencephalography in patients whose initial invasive evaluation with subdural grid electrodes was unsuccessful in localizing seizure origin. METHODS: We conducted a retrospective review of patients who underwent subdural grid evaluation (SDE) at our center and identified patients who underwent a re-evaluation with stereoelectroencephalography (SEEG). RESULTS: We identified three patients who had both subdural and SEEG electrodes in the region of the identified epileptogenic zone in whom the initial SDE evaluation failed to make the patients seizure-free. Two of these patients underwent a second resection and became seizure-free. SIGNIFICANCE: Stereoelectroencephalography can be useful in the re-evaluation and re-operation of patients who previously had surgical failure using SDE.

Determining the role and responsibilities of the community epilepsy nurse in the management of epilepsy.

AIMS AND OBJECTIVES: The aim of this study is to enhance the understanding of the core elements and influencing factors on the community-based epilepsy nurse's role and responsibilities. BACKGROUND: Internationally, epilepsy nurse specialists play a key role in providing person-centred care and management of epilepsy but there is a gap in understanding of their role in the community. DESIGN: A national three-stage, mixed-method study was conducted. METHODS: One-on-one, in-depth semi-structured qualitative interviews were conducted online with 12 community-based epilepsy nurses (Stage 1); retrospective analysis of data collected from the National Epilepsy Line, a nurse-led community helpline (Stage 2); and focus group conducted with four epilepsy nurses, to delve further into emerging findings (Stage 3). A thematic analysis was conducted in Stages 1 and 3, and a descriptive statistical analysis of Stage 2 data. Consolidated Criteria for Reporting Qualitative studies checklist was followed for reporting. RESULTS: Three key themes emerged: (1) The epilepsy nurse career trajectory highlighted a lack of standardised qualifications, competencies, and career opportunities. (2) The key components of the epilepsy nurse role explored role diversity, responsibilities, and models of practice in the management of living with epilepsy, and experiences navigating complex fragmented systems and practices. (3) Shifting work practices detailed the adapting work practices, impacted by changing service demands, including COVID-19 pandemic experiences, role boundaries, funding, and resource availability. CONCLUSION: Community epilepsy nurses play a pivotal role in providing holistic, person-centred epilepsy management They contribute to identifying and addressing service gaps through innovating and implementing change in service design and delivery. RELEVANCE TO CLINICAL PRACTICE: Epilepsy nurses' person-centred approach to epilepsy management is influenced by the limited investment in epilepsy-specific integrated care initiatives, and their perceived value is impacted by the lack of national standardisation of their role and scope of practice. NO PATIENT OR PUBLIC CONTRIBUTION: Only epilepsy nurses' perspectives were sought.

Predictors of longitudinal seizure outcomes after epilepsy surgery in childhood.

There is a paucity of data on longitudinal seizure outcome of children undergoing epilepsy surgery. All children (n = 132) who underwent resective epilepsy surgery from January 1998 to December 2015 were identified. Relevant clinical, neurophysiological, imaging, surgical and seizure outcome data were extracted. Multivariable logistic regression analysis and Kaplan-Meier survival with Cox proportional hazard modelling were performed. The mean age at surgery was 7.8 years (range 0.2-17.9). 71% were seizure-free at a mean follow up of 5.3 ± 2.7 years. Of those who were seizure-free, 65 patients were able to completely wean off anti- seizure medications successfully. Using survival analysis, the probability of Engel Class I outcome at one year after surgery was 81% (95% confidence interval [CI] 87%-75%). This dropped to 73% at two years (95% CI 81%-65%), 58% at five years (95% CI 67.8%-48%), and 47% at ten years. Proportional hazard modelling showed that the presence of moderate to severe developmental disability (HR 6.5; p = 0.02) and lack of complete resection (HR 0.4; p = 0.02) maintain association as negative predictors of seizure-free outcome. Our study demonstrates favorable long-term seizure control following pediatric epilepsy surgery and highlights important predictors of seizure outcome guiding case selection and counseling of expectations prior to surgery.

Investigating the Precise Localization of the Grasping Action in the Mid-Cingulate Cortex and Future Directions.

Objective: To prospectively study the cingulate cortex for the localization and role of the grasping action in humans during electrical stimulation of depth electrodes. Methods: All the patients (n = 23) with intractable focal epilepsy and a depth electrode stereotactically placed in the cingulate cortex, as part of their pre-surgical epilepsy evaluation from 2015 to 2017, were included. Cortical stimulation was performed and examined for grasping actions. Post-implantation volumetric T1 MRIs were co-registered to determine the exact electrode position. Results: Five patients (male: female 4:1; median age 31) exhibited contralateral grasping actions during electrical stimulation. All patients had electrodes implanted in the ventral bank of the right cingulate sulcus adjacent to the vertical anterior commissure (VAC) line. Stimulation of other electrodes in adjacent regions did not elicit grasping. Conclusion: Grasping action elicited from a localized region in the mid-cingulate cortex (MCC) directly supports the concept of the cingulate cortex being crucially involved in the grasping network. This opens an opportunity to explore this region with deep brain stimulation as a motor neuromodulation target for treatment in specific movement disorders or neurorehabilitation.

Localisation and stimulation of the parietal eye field.

Localisation of the human parietal eye fields (PEF) has not been as well studied as the human frontal eye fields (FEF). Stimulation studies in rhesus monkeys have suggested the localisation of the PEF to be within the intraparietal sulcus. Functional MRI studies have demonstrated this region to be highly active and potentially connected in saccadic and gaze shifting tasks. Here, we present a case of a patient with left versive seizures evaluated with SEEG, in whom electrical stimulation within the right intraparietal sulcus resulted in horizontal and downward conjugate eye movements contralateral to stimulation. We illustrate clinical differences between the FEF and PEF on cortical stimulation. In addition to the frontal eye field, it is important to recognise other cortical regions involved in eye movement which can cause conjugate contralateral eye movement.

Determining the role and responsibilities of the Australian epilepsy nurse in the management of epilepsy: a study protocol.

INTRODUCTION: Epilepsy is a common neurological condition affecting between 3% and 3.5% of the Australian population at some point in their lifetime. The effective management of chronic and complex conditions such as epilepsy requires person-centred and coordinated care across sectors, from primary to tertiary healthcare. Internationally, epilepsy nurse specialists are frequently identified as playing a vital role in improving the integration of epilepsy care and enhancing patient self-management. This workforce has not been the focus of research in Australia to date. METHODS AND ANALYSIS: This multistage mixed-method study examines the role and responsibilities of epilepsy nurses, particularly in primary and community care settings, across Australia, including through the provision of a nurse helpline service. A nationwide sample of 30 epilepsy nurses will be purposively recruited via advertisements distributed by epilepsy organisations and through word-of-mouth snowball sampling. Two stages (1 and 3) consist of a demographic questionnaire and semistructured interviews (individual or group) with epilepsy nurse participants, with the thematic data analysis from this work informing the areas for focus in stage 3. Stage 2 comprises of a retrospective descriptive analysis of phone call data from Epilepsy Action Australia's National Epilepsy Line service to identify types of users, their needs and reasons for using the service, and to characterise the range of activities undertaken by the nurse call takers. ETHICS AND DISSEMINATION: Ethics approval for this study was granted by Macquarie University (HREC: 52020668117612). Findings of the study will be published through peer-reviewed journal articles and summary reports to key stakeholders, and disseminated through public forums and academic conference presentations. Study findings will also be communicated to people living with epilepsy and families.

Successful epilepsy surgery for tuberous sclerosis complex evaluated by stereoelectroencephalography.

Evaluating the candidacy for epilepsy surgery in patients with tuberous sclerosis can be challenging, particularly when non-invasive investigations do not show a clear epileptogenic zone. Stereoencephalography may be useful in such cases. We present a case in which the primary epileptogenic tuber was successfully identified by stereoencephalography, which resulted in seizure freedom following epilepsy surgery. [Published with video sequences].

Identification and referral of patients with refractory epilepsy from the primary to the tertiary care interface in New South Wales, Australia.

OBJECTIVES: This mixed-method feasibility study conducted in New South Wales (NSW), Australia, aimed to explore clinical practices around the identification of patients with refractory epilepsy and referral from primary care to Tertiary Epilepsy Centers. The perceptions of general practitioners, neurologists, and adults living with refractory epilepsy were considered. METHODS: Fifty-two data collection events were achieved through 22 semi-structured interviews with six neurologists and 12 adults who currently have, or have had refractory epilepsy, and four family members, 10 clinical observations of patient consultations and 20 surveys with general practitioners. A thematic analysis was conducted on the qualitative data alongside assessment of observational fieldnotes and survey data. FINDINGS: Two main themes emerged: 1) Patient healthcare pathways and care experiences highlighted the complex and deeply contextualized experiences of both patients and healthcare professionals, from first identification of people's seizures, in primary and community care settings, to referral to Tertiary Epilepsy Centers, shedding light on a fragmented, nonstandardized referral process, influenced by both individual and shared-care practices. 2) Factors impacting referrals and patient pathways indicated that onward referral to a Tertiary Epilepsy Center is affected by the knowledge, or the lack thereof, of healthcare professionals regarding treatment options. Barriers include limited person-centered care, shared decision-making, and refractory epilepsy education for healthcare professionals, which can delay patients' disease identification and can hinder speedy referral pathways and processes, in Australia for up to 17 years. In addition, person-centered communication around care pathways is affected by relationships between clinicians, patients, and family members. CONCLUSION: This study has identified a noticeable lack of standardized care across epilepsy-related healthcare sectors, which recognizes a need for developing and implementing clearer epilepsy-related guidelines and Continuing Professional Development in the primary and community care settings. This, however, requires greater collaboration and commitment in the primary, community, and tertiary care sectors to address the ongoing misconceptions around professional roles and responsibilities to optimize shared-care practices. Ultimately, prioritizing person-centered care on both patients' and professionals' agendas, in order to improve satisfaction with care experiences of people living with complex epilepsy.

Course and impact of sleep disturbance in newly diagnosed epilepsy: A prospective registry study.

OBJECTIVE: To determine the course of sleep distrurbance (insomnia symptoms and short sleep duration) after a diagnosis of epilepsy and their associations with seizure control, mood, disability, and quality of life. PATIENTS AND METHODS: One hundred and sixty-nine adults were drawn from the Sydney Epilepsy Incidence Study to Measure Illness Consequences (SEISMIC), a prospective, multicenter, community-wide study in Sydney, Australia. Socio-demographic, psychosocial, clinical characteristics, and information on sleep disturbance were obtained early (median 48 [IQR15-113] days) after a diagnosis of epilepsy, and at 12 months. Logistic regression models were used to determine associations between patterns of sleep disturbance with outcomes at 12 months. RESULTS: Insomnia symptoms and/or short sleep duration were present in 18-23% of participants at both time points, with over half (54-61%) showing a chronic pattern. There was no association of sleep disturbance pattern with recurrent seizures, medication use or disability. Chronic insomnia symptoms and short sleep duration were strongly associated with worse mental health (aOR 3.76, 95% CI 1.28-11.06; and aOR 5.41, 95% CI 1.86-15.79) and poorer quality of life at 12 months (aOR 3.02, 95% CI 1.03-8.84; and aOR 3.11, 95% CI 1.10-8.82), after adjusting for clinical features of epilepsy and comorbidity. Those whose sleep disturbance remitted had no adverse outcomes. CONCLUSIONS: Insomnia symptoms and short sleep duration are less common in people with recently-diagnosed than chronic epilepsy. The temporal association with poor psycholosocial outcomes supports specific interventions addressing sleep disturbance.

Could the 2017 ILAE and the four-dimensional epilepsy classifications be merged to a new "Integrated Epilepsy Classification"?

Over the last few decades the ILAE classifications for seizures and epilepsies (ILAE-EC) have been updated repeatedly to reflect the substantial progress that has been made in diagnosis and understanding of the etiology of epilepsies and seizures and to correct some of the shortcomings of the terminology used by the original taxonomy from the 1980s. However, these proposals have not been universally accepted or used in routine clinical practice. During the same period, a separate classification known as the "Four-dimensional epilepsy classification" (4D-EC) was developed which includes a seizure classification based exclusively on ictal symptomatology, which has been tested and adapted over the years. The extensive arguments for and against these two classification systems made in the past have mainly focused on the shortcomings of each system, presuming that they are incompatible. As a further more detailed discussion of the differences seemed relatively unproductive, we here review and assess the concordance between these two approaches that has evolved over time, to consider whether a classification incorporating the best aspects of the two approaches is feasible. To facilitate further discussion in this direction we outline a concrete proposal showing how such a compromise could be accomplished, the "Integrated Epilepsy Classification". This consists of five categories derived to different degrees from both of the classification systems: 1) a "Headline" summarizing localization and etiology for the less specialized users, 2) "Seizure type(s)", 3) "Epilepsy type" (focal, generalized or unknown allowing to add the epilepsy syndrome if available), 4) "Etiology", and 5) "Comorbidities & patient preferences".

Hospital service utilization trajectories of individuals living with epilepsy in New South Wales, Australia, 2012-2016: A population-based study.

OBJECTIVES: This study aimed to examine five-year trajectories of hospital service utilization among individuals living with epilepsy in New South Wales (NSW), Australia, and to identify factors predictive of trajectory group membership. METHODS: This study used group-based trajectory modeling of hospital admissions over a five-year period for individuals living with epilepsy who had an epilepsy-related hospitalization during 1 January 2012 and 31 December 2012 in NSW, Australia (n = 5762). RESULTS: The analysis revealed the following five distinct hospital service utilization trajectory groups: "one-off users" (Group 1; 22.9%), "low-chronic users" (Group 2; 47.1%), "moderate-declining users" (Group 3; 10.3%), "moderate-chronic users" (Group 4; 18.3%), and "high-chronic users" (Group 5; 1.5%). There were key features that defined trajectory group membership, in particular the relative proportions of group members with chronic health conditions, other comorbid conditions, refractory epilepsy, and status epilepticus. For instance, "high-chronic users" (Group 5) had higher proportions of individuals with chronic health conditions (34.8%) and refractory epilepsy (19.1%); "moderate-declining users" (Group 3) had higher proportions of individuals with chronic health conditions (35.1%) and status epilepticus (9.8%); and "low-chronic users" (Group 2) had the lowest proportion of individuals with chronic health conditions. CONCLUSION: It is important to gain a better understanding of hospital service utilization among individuals living with epilepsy. This research has identified trajectory groups of hospital service utilization profiles of individuals living with epilepsy. Identification of predictors of trajectory group membership allows targeting of strategies to reduce hospital admissions, inform healthcare service delivery, and improve the health and wellbeing of individuals living with epilepsy.

Enhancing quality of life among epilepsy surgery patients: Interlinking multiple social and relational determinants.

BACKGROUND: Achieving seizure control through resective brain surgery is a major predictor of improved quality of life (QOL) among people with refractory (drug-resistant) epilepsy. Nevertheless, QOL is a comprehensive and dynamic construct, consisting of broad dimensions such as physical health, psychosocial well-being, level of independence, social relationships, and beyond. This study highlights the interlinkage and complementarity of these diverse dimensions, and how in practice, patients, clinicians, and others in a social support system can actively promote QOL among surgery patients. METHOD: Twenty-one qualitative in-depth interviews with patients with refractory epilepsy who are either undergoing presurgical assessment or postsurgery follow-up were conducted, to consider their perspective on QOL in relation to their experience of illness and surgical treatment. Data were thematically analyzed, resulting in three key thematic findings. RESULTS: (1) A myriad of QOL dimensions are highly interrelated and interdependent with mutual 'spin-off' effects: Uncontrolled seizures impacted beyond physical and cognitive health, disrupting important social identities such as being successful parents, spouses, and career professionals. The desire for good clinical outcomes from surgery was justified against the need to mitigate these social and personal concerns. (2) In postsurgery care, there were complementary effects of clinical interventions and social factors on patients' QOL. Psychosocial well-being was supported by a combination of improved physical health, self-confidence, psychological interventions, and social support from employers and educators who were sensitive to patients' specialized needs. (3) Engaging in education, employment, and government services influenced not only socioeconomic well-being, but also a sense of social inclusion. Advocacy made on behalf of patients by clinicians and family members has helped to better manage patients' eligibility for social services provision. CONCLUSION: Quality of life is achieved through a comprehensive and interactive social process, and not simply an outcome measure of clinical treatment. The responses and interactions of many others within the patients' life and treatment process, including family members, clinicians, and social service workers, can culminate to influence QOL, highlighting the importance of a relational and social determinants perspective in patient care.

The varied semiology of seizures in the context of small anterior temporal encephaloceles.

Small encephaloceles of the anterior temporal pole have been increasingly recognised as an underlying epileptogenic substrate in patients with medically refractory epilepsy. The current report aims to expand on the current knowledge by emphasising that seizure semiology in such patients can vary significantly. Patients were selected from an epilepsy surgery database between 2012 and 2017. Of the 143 patients who underwent epilepsy surgery, six patients had a temporal encephalocele. Four of these patients had stereo-EEG implantation. Of the four patients studied, each had a seizure semiology discordant with an ictal focus in the temporal lobe. Intracranial EEG assessment demonstrated, irrespective of this semiology, seizures originated from the anterior temporal pole. Seizures were observed to rapidly propagate to the orbitofrontal cortex, insula, temporo-occipital junction, and posterior language regions. Engagement of the mesial temporal structures could occur early or late, however, a good surgical outcome was achieved following a focused lesionectomy in either situation. The major finding was that seizures arising from anterior temporal encephaloceles can have an extra-temporal semiology. The varied clinical semiology and the rapid propagation to seemingly distant cortical regions could be explained by the connectivity of the anterior temporal lobe.

A study of perfusion changes with Insula Epilepsy using SPECT.

PURPOSE: The non-invasive localisation of insular lobe epilepsy is a challenge. We aimed to determine if ictal SPECT is a reliable adjunctive test in insular cases and to explore its role in the tailoring of intracranial strategies. METHOD: From a dataset of patients who underwent SEEG between December 2012 and December 2016, we collected patients with focal insular onset epilepsy. We examined semiology, EEG, PET and SPECT hyperperfusion pattern with SISCOM. We also reviewed relevant literature. RESULTS: 5 patients were identified, 4 females, from a dataset of 51 patients. Median age of seizure onset was 8 years old (8 months to 10 years). All patients had an ictal SPECT during pre-surgical work-up: median injection time was 7 s (3-17 sec) from clinical onset, and median seizure duration was 42 s (11-85 sec). Insula cortex showed focal hyperaemia in four patients, all bilateral, with the greatest hyperperfusion contralateral to the ictal onset in two cases, using SISCOM threshold at 1.5 standard deviation. Other sites with hyperaemia included basal ganglia and middle temporal gyrus. The SEEG confirmed insular onset seizures in all the cases. All patients had epilepsy surgery and were seizure free at 21 to 50 months follow up. The results from the literature review showed frequent hyperperfusion in structures outside insula and frequently over the contralateral hemisphere. CONCLUSIONS: This study highlights the technical limitations of SPECT when attempting to assess seizures arising from the insula. Our findings and the literature show ictal SPECT can be localising but falsely lateralising in seizures arising from the insula.

Critique of the 2017 epileptic seizure and epilepsy classifications.

This article critiques the International League Against Epilepsy (ILAE) 2015-2017 classifications of epilepsy, epileptic seizures, and status epilepticus. It points out the following shortcomings of the ILAE classifications: (1) they mix semiological terms with epileptogenic zone terminology; (2) simple and widely accepted terminology has been replaced by complex terminology containing less information; (3) seizure evolution cannot be described in any detail; (4) in the four-level epilepsy classification, level two (epilepsy category) overlaps almost 100% with diagnostic level one (seizure type); and (5) the design of different classifications with distinct frameworks for newborns, adults, and patients in status epilepticus is confusing. The authors stress the importance of validating the new ILAE classifications and feel that the decision of Epilepsia to accept only manuscripts that use the ILAE classifications is premature and regrettable.

Disability patterns over the first year after a diagnosis of epilepsy.

OBJECTIVE: To determine the patterns and predictors of disability over the first 12 months after a diagnosis of epilepsy. PATIENTS AND METHODS: The Sydney Epilepsy Incidence Study to Measure Illness Consequences (SEISMIC) was a prospective, multicenter, community-based study of people with newly diagnosed epilepsy in Sydney, Australia. Disability was assessed using the World Health Organization's, Disability Assessment Schedule (WHODAS) 2.0 12-item version, at baseline (i.e. within 28 days of diagnosis) and 12 months post-diagnosis. Demographic, socioeconomic, clinical and epilepsy-related data, obtained through structured interviews, were entered into multivariable linear regression and shift analysis to determine predictors of greater disability. RESULTS: Of 259 adults (≥18 years), 190 (73%) had complete WHODAS at baseline (mean ± SD scores 4 ± 6) and follow-up (4 ± 8). After adjustment for age, sex and co-morbidity, greater overall disability at 12 months was associated with lower education (P = 0.05), economic hardship (P = 0.004), multiple antiepileptic medications (P = 0.02) and greater disability (P < 0.001) at the time of diagnosis; these variables explained 38.3% of the variance. Among the 12 WHODAS items, "being emotionally affected by health problems" was the most frequent disability problem identified at both time points (all P < 0.0001). The proportion of participants without problems in that domain improved over 12 months (from 24% to 50%, P < 0.0001), whereas the other 11 items remained relatively stable. Independent baseline predictors of a worse emotional outcome at 12 months were severe/extreme emotional distress (odds ratio [OR] 4.52, 95% confidence intervals [CI] 1.67-12.24), economic hardship (OR 2.30, 95% CI 1.24-4.25) and perceived stigma (OR 2.02, 95% CI 1.03-3.93). CONCLUSION: Most people report problems with emotional health after a diagnosis of epilepsy but many recover over the next 12 months. Services addressing the social and psychological impact of diagnosis may be needed to improve outcome.