Publications by authors named "Wendyl d'Souza"

Introduction: The autoimmune encephalitides (AE) are a heterogeneous group of neurological disorders with significant morbidity and healthcare costs. Despite advancements in understanding their pathophysiology, uncertainties persist regarding long-term prognosis and optimal management. This study aims to address these gaps, focusing on immunotherapeutic strategies, neoplastic associations and functional outcomes.

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Background And Objectives: Stereo-EEG-guided radiofrequency thermocoagulation (RFTHC) has been proposed as relatively safe from a cognitive perspective; however, there is a lack of evidence based on neuropsychological assessments supporting this. This study is the first prospective evaluation of neuropsychological outcomes associated with stereo-EEG-guided RFTHC in patients with focal drug-resistant epilepsy.

Methods: This cohort study involved prospective recruitment of consecutive patients undergoing stereo-EEG from 2 Australian centers.

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This analysis assessed the effectiveness and tolerability of brivaracetam (BRV) in older (≥65 years of age) and younger (≥16 to <65 years of age) adults with epilepsy. This was a subgroup analysis from EXPERIENCE/EPD332, a pooled analysis of individual patient records from multiple independent, non-interventional studies of patients with epilepsy starting BRV in Australia, Europe, and the United States. Included patients had ≥6 months of follow-up data.

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Objective: Over recent years, there has been a growing interest in exploring the utility of seizure risk forecasting, particularly how it could improve quality of life for people living with epilepsy. This study reports on user experiences and perspectives of a seizure risk forecaster app, as well as the potential impact on mood and adjustment to epilepsy.

Methods: Active app users were asked to complete a survey (baseline and 3-month follow-up) to assess perspectives on the forecast feature as well as mood and adjustment.

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Genetic factors contribute to the aetiology of epilepsy in >50% of cases, and information on the use of antiseizure medications in people with specific aetiologies will help guide treatment decisions. The PERMIT Extension study pooled data from two real-world studies (PERMIT and PROVE) to investigate the effectiveness and safety/tolerability of perampanel (PER) when used to treat people with focal and generalised epilepsy in everyday clinical practice. This post-hoc analysis of PERMIT Extension explored the use of PER when used to treat individuals presumed to have epilepsy with a genetic aetiology.

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Objective: To assess the effectiveness and tolerability of brivaracetam (BRV) in adults with epilepsy by specific comorbidities and epilepsy etiologies.

Methods: EXPERIENCE/EPD332 was a pooled analysis of individual patient records from several non-interventional studies of patients with epilepsy initiating BRV in clinical practice. Outcomes included ≥ 50% reduction from baseline in seizure frequency, seizure freedom (no seizures within prior 3 months), continuous seizure freedom (no seizures since baseline), BRV discontinuation, and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months.

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Article Synopsis
  • Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy, and new diagnostic criteria have been developed by the International League Against Epilepsy (ILAE) to help identify it more accurately.
  • In a study involving 60 patients diagnosed with LGS through video-EEG monitoring, only 48% met the new ILAE diagnostic criteria, indicating that many could have been misdiagnosed under previous standards.
  • The findings emphasize the importance of using modern ILAE criteria for more accurate LGS diagnosis, particularly given the different clinical features and outcomes among those who did and did not meet these standards.
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Epilepsy is a serious neurological disorder characterised by a tendency to have recurrent, spontaneous, seizures. Classically, seizures are assumed to occur at random. However, recent research has uncovered underlying rhythms both in seizures and in key signatures of epilepsy-so-called interictal epileptiform activity-with timescales that vary from hours and days through to months.

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Article Synopsis
  • The study investigates the neuropsychological effects of psychosis in patients with epilepsy (POE), highlighting structural issues in brain networks responsible for cognitive functions.
  • Twelve POE patients were compared to epilepsy patients without psychosis and healthy controls to assess their performance on memory and executive function tests.
  • Results indicated that POE patients performed the worst across cognitive tasks, particularly in working memory, verbal recall, and cognitive control, compared to the other groups.
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Background And Objective: Real-world evidence studies of brivaracetam (BRV) have been restricted in scope, location, and patient numbers. The objective of this pooled analysis was to assess effectiveness and tolerability of brivaracetam (BRV) in routine practice in a large international population.

Methods: EXPERIENCE/EPD332 was a pooled analysis of individual patient records from multiple independent non-interventional studies of patients with epilepsy initiating BRV in Australia, Europe, and the United States.

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Objective: To assess the effectiveness and safety/tolerability of perampanel (PER) in people with epilepsy (PWE) treated in everyday clinical practice for focal and generalized seizures, both in the total cohort and by age group.

Methods: The PERMIT Extension study was a pooled analysis of data from PWE included in two large previous clinical practice studies (PERMIT and PROVE). Retention was assessed over 12 months.

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Purpose: To quantify sponsor-reported shortages of oral antiseizure medications in Australia, estimate the number of patients impacted, and the association between shortages and brand or formulation switching, and changes in adherence.

Methods: A retrospective cohort study of sponsor-reported shortages (defined as where the supply of a medicine will not or will not be likely to meet the demand over a 6-month period) of antiseizure medications reported to the Medicine Shortages Reports Database (Therapeutic Goods Administration, Australia); cross-referencing shortages to the IQVIA-NostraData Dispensing Data (LRx) database, a deidentified, population-level dataset collecting longitudinal dispensation data on individual patients from ∼75% of Australian community pharmacy scripts.

Results: Ninety-seven sponsor-reported ASM shortages were identified between 2019 and 2020; of those, 90 (93%) were shortages of generic ASM brands.

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Objective: Well-being and quality of life can vary independently of disease. Instruments measuring well-being and quality of life are commonly used in neurology, but there has been little investigation into the extent in which they accurately measure wellbeing/quality of life or if they merely reflect a diseased state of an individual.

Design: Systematic searches, thematic analysis and narrative synthesis were undertaken.

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Objective: This study aims to determine the contribution of comorbidities to excess psychogenic nonepileptic seizures (PNES) mortality.

Methods: A retrospective cohort study was conducted of tertiary epilepsy outpatients from St. Vincent's Hospital Melbourne, Australia with an 8:1 comparison cohort, matched by age, sex, and socioeconomic status (SES) to national administrative databases between 2007 and 2017.

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Objective: In vitro data prompted U.S Food and Drug Administration warnings that lamotrigine, a common sodium channel modulating anti-seizure medication (NaM-ASM), could increase the risk of sudden death in patients with structural or ischaemic cardiac disease, however, its implications for Sudden Unexpected Death in Epilepsy (SUDEP) are unclear.

Methods: This retrospective, nested case-control study identified 101 sudden unexpected death in epilepsy (SUDEP) cases and 199 living epilepsy controls from Epilepsy Monitoring Units (EMUs) in Australia and the USA.

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Objectives: Despite the prevalence of cognitive symptoms in the idiopathic generalized epilepsies (IGEs), cognitive dysfunction in juvenile absence epilepsy (JAE), a common yet understudied IGE subtype, remains poorly understood. This descriptive study provides a novel, comprehensive characterization of cognitive functioning in a JAE sample and examines the relationship between cognition and 24-h epileptiform discharge load.

Method: Forty-four individuals diagnosed with JAE underwent cognitive assessment using Woodcock Johnson III Test of Cognitive Abilities with concurrent 24-h ambulatory EEG monitoring.

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Objective: Medication adherence is considered an important risk factor for sudden unexpected death in epilepsy (SUDEP), although measurement accuracy is difficult. Using prescription dispensations, this study aims to estimate antiseizure medication (ASM) adherence and identify adherence patterns that influence epilepsy mortality.

Methods: This is a retrospective cohort study of tertiary epilepsy outpatients seen at St Vincent's Hospital Melbourne, Victoria, Australia, from January 1, 2012 until December 31, 2017.

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Sleep duration, sleep deprivation and the sleep-wake cycle are thought to play an important role in the generation of epileptic activity and may also influence seizure risk. Hence, people diagnosed with epilepsy are commonly asked to maintain consistent sleep routines. However, emerging evidence paints a more nuanced picture of the relationship between seizures and sleep, with bidirectional effects between changes in sleep and seizure risk in addition to modulation by sleep stages and transitions between stages.

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Objective: To examine the utility of neuroimaging characteristics as biomarkers of prognosis in seropositive autoimmune encephalitis (AE).

Methods: In this multi-center study, we retrospectively analyzed 66 cases of seropositive AE. The MRI and PET imaging was assessed by independent visual inspection.

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Background: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment.

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Objective: To explore the cortical morphological associations of the psychoses of epilepsy.

Methods: Psychosis of epilepsy (POE) has two main subtypes - postictal psychosis and interictal psychosis. We used automated surface-based analysis of magnetic resonance images to compare cortical thickness, area, and volume across the whole brain between: (i) all patients with POE (n = 23) relative to epilepsy-without psychosis controls (EC; n = 23), (ii) patients with interictal psychosis (n = 10) or postictal psychosis (n = 13) relative to EC, and (iii) patients with postictal psychosis (n = 13) relative to patients with interictal psychosis (n = 10).

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Background: Focal semiologies have been described in idiopathic generalized epilepsies (IGE) and generalized-onset bilateral tonic-clonic seizures (GBTCS). These focal signs may lead to wrong diagnosis and inappropriate choice of antiseizure medications. We sought to investigate the differences in focal semiologic features between GBTCS and focal-onset bilateral tonic-clonic seizures (FBTCS).

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Purpose: To investigate the effectiveness, safety and tolerability of perampanel (PER) in treating myoclonic seizures in clinical practice, using data from the PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study.

Methods: PERMIT was a pooled analysis of 44 real-world studies from 17 countries, in which patients with focal and generalised epilepsy were treated with PER. This post-hoc analysis included patients with myoclonic seizures at baseline.

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Autoimmune encephalitis (AE) is a neurological disorder caused by autoimmune attack on cerebral proteins. Experts currently recommend staged immunotherapeutic management, with first-line immunotherapy followed by second-line immunotherapy if response to first-line therapy is inadequate. Meta-analysis of the evidence base may provide higher quality evidence to support this recommendation.

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Objective: To evaluate the prevalence and biomarkers of drug-resistant epilepsy (DRE) in patients with autoimmune encephalitis (AIE).

Methods: Sixty-nine patients with AIE were recruited retrospectively and electroencephalographies (EEGs) were reviewed using a standard reporting proforma. Associations between EEG biomarkers and DRE development at 12 months were examined using logistic regression modeling and were utilized to create a DRE risk score.

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