Recovery From Homonymous Hemianopia in Hyperglycemia-Induced Occipital Lobe Electroclinical Seizures Following Glycemic Control.

BACKGROUND: Visual changes due to hyperglycemia in diabetes are not uncommon. While blurred vision is a well-established sequela of chronic hyperglycemia, homonymous hemianopia with or without electroclinical seizures is much rarer and can be mistaken for migraine, temporal arteritis, or ischemia of the central nervous system. METHODS: This article analyzed case studies for 3 patients (67M, 68M, 52F) presenting with complex visual phenomena, from 3 to 42 days duration, including pathogenesis, clinical findings, management, and follow-up. RESULTS: Examinations demonstrated dense left homonymous hemianopias in 2 patients and a left inferior homonymous quadrantanopia in one, with no other abnormalities. Patients described vivid, nonstereotyped intermittent hallucinations in the affected fields. Blood glucose levels ranged from 13.5 to 35.0 mmol/L (243-630 mg/dL) without ketosis and HbA1c from 14.6% to 16.8%. Computed tomography of the brain showed no acute intracranial pathology. MRI of the brain either detected no abnormalities or demonstrated changes consistent with seizure activity. Electroencephalogram (EEG) demonstrated seizures over the right occipital region in each patient. EEG seizures coincided with patients' hallucinations, while they remained otherwise conscious. Oral hypoglycemic and antiepileptic medications were commenced with rapid and complete reversal of the seizures and visual field deficits, confirmed by repeat Automated 30-2 and MRI. CONCLUSIONS: Hyperglycemia-induced occipital lobe seizures with visual hallucinations and interictal homonymous visual field defects represent a rare but clinically important diagnosis. This article highlights the importance of prompt recognition and treatment to facilitate recovery.

Which terms should be used to describe medications used in the treatment of seizure disorders? An ILAE position paper.

A variety of terms, such as "antiepileptic," "anticonvulsant," and "antiseizure" have been historically applied to medications for the treatment of seizure disorders. Terminology is important because using terms that do not accurately reflect the action of specific treatments may result in a misunderstanding of their effects and inappropriate use. The present International League Against Epilepsy (ILAE) position paper used a Delphi approach to develop recommendations on English-language terminology applicable to pharmacological agents currently approved for treating seizure disorders. There was consensus that these medications should be collectively named "antiseizure medications". This term accurately reflects their primarily symptomatic effect against seizures and reduces the possibility of health care practitioners, patients, or caregivers having undue expectations or an incorrect understanding of the real action of these medications. The term "antiseizure" to describe these agents does not exclude the possibility of beneficial effects on the course of the disease and comorbidities that result from the downstream effects of seizures, whenever these beneficial effects can be explained solely by the suppression of seizure activity. It is acknowledged that other treatments, mostly under development, can exert direct favorable actions on the underlying disease or its progression, by having "antiepileptogenic" or "disease-modifying" effects. A more-refined terminology to describe precisely these actions needs to be developed.

The efficacy and tolerability of adjunctive brivaracetam for the treatment of adult epilepsy: An Australian multi-center retrospective real-world observational cohort study.

OBJECTIVE: Assess the efficacy and tolerability of add-on therapy brivaracetam (BRV) in adult patients with epilepsy in a real-world setting. METHODS: This multi-center retrospective observational cohort study examined all adult patients who commenced on BRV at 11 Australian epilepsy centers between 2017 and 2020. Primary outcomes were seizure response (≥50% reduction in frequency) and seizure freedom 12 months post BRV commencement, and tolerability. We report three approaches to missing data (complete case analysis, CCA; last observation carried forward, LOCF; and intention to treat, ITT). Secondary outcomes included the durability of early BRV response and continuous seizure freedom from BRV initiation. Subgroup analysis examined patients with focal and generalized epilepsy and patients with refractory (≥4 prior ASMs) and highly refractory (≥7 prior ASMs) epilepsy. Outcomes were also assessed at 'personalized' seizure outcome time points based on baseline seizure frequency. RESULTS: Baseline and follow-up data were available for 228 patients. The mean age was 41.5 years (IQR 30, 50). Most had focal epilepsy (188/228, 82.5%). Median number of previous ASMs was 4 (2, 7), and concomitant ASMs 2 (2, 3). Twelve-month responder rate was: 46.3% using CCA (95% CI 34.0, 58.9); 39.5% using LOCF (33.1, 46.1); and 15.4% using ITT (10.9, 20.7). Twelve-month seizure freedom was: 23.9% using CCA (14.3, 35.9); 24.6% using LOCF (19.1, 30.7); and 7.9% using ITT (4.7, 12.1). The most frequent adverse effects were sedation or cognitive slowing (33/228, 14.5%), irritability or aggression (16/228, 7.0%), and low mood (14/228, 6.1%). Outcomes were similar using continuous outcome definitions and 'personalized' outcome assessment time points. Early responses were highly durable, with 3-month response maintained at all subsequent time points at 83%, and seizure freedom maintained at 85%. Outcomes were similar in focal (n = 187) and generalizsed (n = 25) subgroups. Outcomes were similar in refractory patients (n = 129), but lower in the highly refractory group (n = 62), however improvement with BRV was still observed with 12-month seizure freedom of 8.3% using CCA (1.0, 27), 6.5% using LOCF (1.8, 15.7); and 3.2% using ITT (0.4, 11.2). CONCLUSIONS: Meaningful real-world responder and seizure freedom rates can be still observed in a refractory epilepsy population. Brivaracetam response can occur early and appears to be maintained with minimal later relapse. The results should be interpreted with caution given the retrospective nature of the study and the quantities of missing data at later time points.

Mood and Anxiety Disorders and Suicidality in Patients With Newly Diagnosed Focal Epilepsy: An Analysis of a Complex Comorbidity.

BACKGROUND AND OBJECTIVES: Mood, anxiety disorders, and suicidality are more frequent in people with epilepsy than in the general population. Yet, their prevalence and the types of mood and anxiety disorders associated with suicidality at the time of the epilepsy diagnosis are not established. We sought to answer these questions in patients with newly diagnosed focal epilepsy and to assess their association with suicidal ideation and attempts. METHODS: The data were derived from the Human Epilepsy Project study. A total of 347 consecutive adults aged 18-60 years with newly diagnosed focal epilepsy were enrolled within 4 months of starting treatment. The types of mood and anxiety disorders were identified with the Mini International Neuropsychiatric Interview, whereas suicidal ideation (lifetime, current, active, and passive) and suicidal attempts (lifetime and current) were established with the Columbia Suicidality Severity Rating Scale (CSSRS). Statistical analyses included the t test, χ2 statistics, and logistic regression analyses. RESULTS: A total of 151 (43.5%) patients had a psychiatric diagnosis; 134 (38.6%) met the criteria for a mood and/or anxiety disorder, and 75 (21.6%) reported suicidal ideation with or without attempts. Mood (23.6%) and anxiety (27.4%) disorders had comparable prevalence rates, whereas both disorders occurred together in 43 patients (12.4%). Major depressive disorders (MDDs) had a slightly higher prevalence than bipolar disorders (BPDs) (9.5% vs 6.9%, respectively). Explanatory variables of suicidality included MDD, BPD, panic disorders, and agoraphobia, with BPD and panic disorders being the strongest variables, particularly for active suicidal ideation and suicidal attempts. DISCUSSION: In patients with newly diagnosed focal epilepsy, the prevalence of mood, anxiety disorders, and suicidality is higher than in the general population and comparable to those of patients with established epilepsy. Their recognition at the time of the initial epilepsy evaluation is of the essence.

Methodology for classification and definition of epilepsy syndromes with list of syndromes: Report of the ILAE Task Force on Nosology and Definitions.

Epilepsy syndromes have been recognized for >50 years, as distinct electroclinical phenotypes with therapeutic and prognostic implications. Nonetheless, no formally accepted International League Against Epilepsy (ILAE) classification of epilepsy syndromes has existed. The ILAE Task Force on Nosology and Definitions was established to reach consensus regarding which entities fulfilled criteria for an epilepsy syndrome and to provide definitions for each syndrome. We defined an epilepsy syndrome as "a characteristic cluster of clinical and electroencephalographic features, often supported by specific etiological findings (structural, genetic, metabolic, immune, and infectious)." The diagnosis of a syndrome in an individual with epilepsy frequently carries prognostic and treatment implications. Syndromes often have age-dependent presentations and a range of specific comorbidities. This paper describes the guiding principles and process for syndrome identification in both children and adults, and the template of clinical data included for each syndrome. We divided syndromes into typical age at onset, and further characterized them based on seizure and epilepsy types and association with developmental and/or epileptic encephalopathy or progressive neurological deterioration. Definitions for each specific syndrome are contained within the corresponding position papers.

ILAE definition of the Idiopathic Generalized Epilepsy Syndromes: Position statement by the ILAE Task Force on Nosology and Definitions.

In 2017, the International League Against Epilepsy (ILAE) Classification of Epilepsies described the "genetic generalized epilepsies" (GGEs), which contained the "idiopathic generalized epilepsies" (IGEs). The goal of this paper is to delineate the four syndromes comprising the IGEs, namely childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and epilepsy with generalized tonic-clonic seizures alone. We provide updated diagnostic criteria for these IGE syndromes determined by the expert consensus opinion of the ILAE's Task Force on Nosology and Definitions (2017-2021) and international external experts outside our Task Force. We incorporate current knowledge from recent advances in genetic, imaging, and electroencephalographic studies, together with current terminology and classification of seizures and epilepsies. Patients that do not fulfill criteria for one of these syndromes, but that have one, or a combination, of the following generalized seizure types: absence, myoclonic, tonic-clonic and myoclonic-tonic-clonic seizures, with 2.5-5.5 Hz generalized spike-wave should be classified as having GGE. Recognizing these four IGE syndromes as a special grouping among the GGEs is helpful, as they carry prognostic and therapeutic implications.

International League Against Epilepsy classification and definition of epilepsy syndromes with onset at a variable age: position statement by the ILAE Task Force on Nosology and Definitions.

The goal of this paper is to provide updated diagnostic criteria for the epilepsy syndromes that have a variable age of onset, based on expert consensus of the International League Against Epilepsy Nosology and Definitions Taskforce (2017-2021). We use language consistent with current accepted epilepsy and seizure classifications and incorporate knowledge from advances in genetics, electroencephalography, and imaging. Our aim in delineating the epilepsy syndromes that present at a variable age is to aid diagnosis and to guide investigations for etiology and treatments for these patients.

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.

Chronic methyl bromide toxicity is ameliorated by haemodialysis.

Methyl bromide is an odourless, colourless, highly volatile gas, primarily used in fumigation. It can cause significant neurotoxicity, especially with chronic exposure. Haemodialysis has been used in acute toxicity, but its utility in chronic exposure has never been reported. We report the use of haemodialysis in a 20-year-old man with chronic methyl bromide toxicity affecting the optic nerves, brain and spinal cord. The patient underwent eight haemodialysis sessions with improvement in plasma bromine concentration, half-life and marked clinical recovery. The case demonstrates the utility of haemodialysis in the treatment of chronic methyl bromide toxicity.

Prevalence of Driving and Traffic Accidents among People with Seizures: A Systematic Review.

BACKGROUND AND OBJECTIVES: Epilepsy influences the ability to drive. We undertook a systematic review to determine the prevalence of driving or holding a driver's license among people with seizures, the prevalence of traffic accidents among those who drive, and factors that may explain heterogeneity in these point estimates. METHOD: We followed MOOSE and PRISMA guidelines in searching 8 databases from inception to June 27, 2018. All published observational studies were included, with the exception of case-control studies where prevalence could not be determined, case reports, and studies with fewer than 50 participants. We assessed external and internal validity and quality of studies, produced forest plots, and conducted meta-regression in "Stata 13." RESULTS: Data were available from 67 studies published between 1967 and 2018. Across the studies there was a wide range in the prevalence of driving (3-90%) and holding a driver's license (8-98%). Up to 39% of people with epilepsy drove in violation of restrictions. Prevalence of traffic accidents ranged from 0 to 61% following seizure onset, or in the past 1-5 years. The percentage of people with seizures who drove decreased as time since diagnosis increased (p = 0.01, adjusted R2 = 31%). The number of people with seizures who drove or held a driver's license appears to have increased over time (p = 0.02, adjusted R2 = 7%) but without a corresponding increase in the number of traffic accidents. There was considerable heterogeneity between studies related to definitions, design, and population differences. CONCLUSIONS: There is considerable variation in the prevalence of driving after a diagnosis of epilepsy and in reported motor vehicle accidents. Further efforts are required to better understand the impact of epilepsy, and epilepsy surgery, on driving and road safety, especially where driving continues in violation of restrictions. Policy changes are needed to encourage the introduction of available and affordable alternatives for driving, for example, developing public transport networks, and promoting subsidy schemes to encourage use of public transport, taxis, Uber, and Lyft, among people experiencing seizures.

A decision tree to determine fitness to drive in epilepsy: Results of a pilot in two Australian states.

OBJECTIVE: Certification by treating physicians of fitness to drive in people with epilepsy creates a conflict of interest that may result in unsafe decisions, damage the doctor-patient relationship, expose the physician to legal liability and prevent optimal treatment. Ideally, the treating physician should provide objective clinical information to the driver licensing authority (DLA), which then determines fitness or otherwise. However, DLAs in Australia do not employ medical staff and the national standards are complex. Fitness is determined by the treating physician, according to published national standards. The purpose of this study was to determine the feasibility of using a decision tree to determine fitness, according to the Australian standards. METHODS: A decision tree was constructed to use clinical data to determine whether a patient met the national standard to drive a private motorcar, failed to meet it or required further assessment. A form was designed to collect the necessary clinical data from the treating physician. A computerized version of the decision tree was then used in a pilot in two Australian states in parallel with the existing certification system. Four hundred thirty-nine drivers with declared epilepsy and their treating physicians were invited to participate when their annual driver licence review was due. RESULTS: Two hundred fifty-three (58%) forms were returned. All patients were considered fit to drive by their physician. Seventy-six percent had not had a seizure for over two years. In 88.1%, there was agreement between the decision tree and treating physician, with 3.6% identified by the decision tree as requiring review. Although considered fit by their physician, 6.3% did not meet the national standard to drive. SIGNIFICANCE: The decision tree model is a practical alternative to fitness certification by treating physicians. This Australian pilot can serve as a model for applying objective standards to driving assessments in other jurisdictions, using local driving standards. It has the potential to improve road safety by avoiding the negative effects of certification by treating physicians and can cope with complex standards. It is now in use in two states of Australia.

Who is driving and who is prone to have traffic accidents? A systematic review and meta-analysis among people with seizures.

INTRODUCTION: Epilepsy influences the ability to drive. We aimed to systematically summarize factors associated with driving, holding a driver's license, and traffic accidents among people with seizures. MATERIAL AND METHODS: Eight databases were searched (from their inception to 27 June 2018). We included all published observational studies, except for case reports and studies with fewer than 50 participants. Pooled mean differences and pooled risk ratios (pRRs) with corresponding confidence intervals (CIs) were calculated using random effects. RESULTS: Data were available from 18 studies, reporting a wide range of factors. There were frequent biases associated with cross-sectional study designs, selection bias, poor statistical quality, small samples, and lack of validation of models. The following six variables were consistently associated with driving: male gender (pRR: 1.42; 95% CI: 1.23 to 1.64), being in paid work (pRR: 1.72; 95% CI: 1.46 to 2.03), married (pRR: 1.26; 95% CI: 1.01 to 1.57), older age at seizure onset or diagnosis (pooled mean difference: 4.83; 95% CI: 0.48 to 9.18 years), less frequent seizures (fewer than monthly, pRR: 1.32; 95% CI: 1.12 to 1.56), and taking one or no antiepileptic drug (pRR: 1.34; 95% CI: 1.09 to 1.63). Lower seizure frequency was also protective for avoiding traffic accidents (pRR: 0.26; 95% CI: 0.10 to 0.66). DISCUSSION: Stable multivariate models to predict driving or traffic accidents among people with seizures have not yet been developed. Current evidence shows that the likelihood of driving is associated with demographic and epilepsy-related factors, while the risk of traffic accidents is associated with seizure frequency.

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.

Return to driving after a diagnosis of epilepsy: A prospective registry study.

OBJECTIVE: To determine the frequency and predictors of return to driving within 1 year after a diagnosis of epilepsy. METHODS: SEISMIC (the Sydney Epilepsy Incidence Study to Measure Illness Consequences) was a prospective, multicenter, community-wide study of people of all ages with newly diagnosed epilepsy in Sydney, Australia. Demographic, socioeconomic, and clinical characteristics and driving status were obtained as soon as possible after baseline registration with a diagnosis of epilepsy. Multivariate logistic regression was used to determine predictors of return to driving at 12-month follow-up. RESULTS: Among 181 (76%) adult participants (≥18 years old) who reported driving before an epilepsy diagnosis, 152 provided information on driving at 12 months, of whom 118 (78%) had returned to driving. Driving for reasons of getting to work or place of education (odds ratio [OR] = 4.70, 95% confidence intervals [CI] = 1.87-11.86), no seizure recurrence (OR = 5.15, 95% CI = 2.07-12.82), and being on no or a single antiepileptic drug (OR = 4.54, 95% CI = 1.45-14.22) were associated with return to driving (C statistic = 0.79). More than half of participants with recurrent seizures were driving at follow-up. SIGNIFICANCE: Early return to driving after a diagnosis of epilepsy is related to work/social imperatives and control of seizures, but many people with recurrent seizures continue to drive. Further efforts are required to implement driving restriction policies and to provide transport options for people with epilepsy.

The importance of early immunotherapy in patients with faciobrachial dystonic seizures.

Faciobrachial dystonic seizures and limbic encephalitis closely associate with antibodies to leucine-rich glioma-inactivated 1 (LGI1). Here, we describe 103 consecutive patients with faciobrachial dystonic seizures and LGI1 antibodies to understand clinical, therapeutic and serological differences between those with and without cognitive impairment, and to determine whether cessation of faciobrachial dystonic seizures can prevent cognitive impairment. The 22/103 patients without cognitive impairment typically had normal brain MRI, EEGs and serum sodium levels (P < 0.0001). Overall, cessation of faciobrachial dystonic seizures with antiepileptic drugs alone occurred in only 9/89 (10%) patients. By contrast, 51% showed cessation of faciobrachial dystonic seizures 30 days after addition of immunotherapy (P < 0.0001), with earlier cessation in cognitively normal patients (P = 0.038). Indeed, expedited immunotherapy (P = 0.031) and normal cognition (P = 0.0014) also predicted reduced disability at 24 months. Furthermore, of 80 patients with faciobrachial dystonic seizures as their initial feature, 56% developed cognitive impairment after 90 days of active faciobrachial dystonic seizures. Whereas only one patient developed cognitive impairment after cessation of faciobrachial dystonic seizures (P < 0.0001). All patients had IgG4-LGI1 antibodies, but those with cognitive impairment had higher proportions of complement-fixing IgG1 antibodies (P = 0.03). Both subclasses caused LGI1-ADAM22 complex internalization, a potential non-inflammatory epileptogenic mechanism. In summary, faciobrachial dystonic seizures show striking time-sensitive responses to immunotherapy, and their cessation can prevent the development of cognitive impairment.awx323media15681705685001.

Frequency and predictors of psychological distress after a diagnosis of epilepsy: A community-based study.

OBJECTIVE: The objective of the study was to determine the frequency and predictors of psychological distress after a diagnosis of epilepsy. METHODS: The Sydney Epilepsy Incidence Study to Measure Illness Consequences (SEISMIC) was a prospective, multicenter, community-based study of people of all ages with newly diagnosed epilepsy in Sydney, Australia. Analyses involved multivariate logistic regression and multinomial logit regression to identify predictors of psychological distress, assessed using the Hospital Anxiety and Depression Scale (HADS) and the Strengths and Difficulties Questionnaire (SDQ), as part of structured interviews. RESULTS: Psychological distress occurred in 33% (95% confidence interval [CI] 26 to 40%) and 24% (95% CI 18 to 31%) of 180 adults at baseline and 12months, respectively, and 23% (95% CI 14 to 33%) of 77 children at both time points. Thirty adults and 7 children had distress at baseline who recovered at 12months, while 15 adults and 7 children had new onset of distress during this period. History of psychiatric or behavioral disorder (for adults, odds ratio [OR] 6.82, 95% CI 3.08 to 15.10; for children, OR 28.85, 95% CI 2.88 to 288.60) and higher psychosocial disability (adults, OR 1.17, 95% CI 1.07 to 1.27) or lower family functioning (children, OR 1.80, 95% CI 1.08 to 3.02) were associated with psychological distress (C statistics 0.80 and 0.78). CONCLUSIONS: Psychological distress is common and fluctuates in frequency after a diagnosis of epilepsy. Those with premorbid psychological, psychosocial, and family problems are at high risk of this adverse outcome.