Epilepsy is one of the most common neurological diseases in the world, but it is also complex and difficult to study. There is a significant genetic component to epilepsy and more information is being published frequently. It is difficult to group and summarise all of this information in a way that is beneficial for both researchers and clinicians. The aim of this paper is to create a summary of all currently known epilepsy associated genes in order to aid epilepsy research to better understand the aetiology of the disease. This was achieved through gathering genetic data from three databases: Online Mendelian Inheritance in Man (OMIM), Clincal Genome (ClinGen), and PubMed. Genes were filtered based on specific criteria and were summarised into three tables: Epilepsy genes, Epilepsy associated genes and Predicted epilepsy associated genes. A fourth table was produced to showcase all epilepsy genes that were identified in all three databases. A total of 2,536 genes were identified to have some level of association with epilepsy. A total of 238 genes were classified as Epilepsy genes, 1,317 genes were classified as Epilepsy associated genes and 981 genes were classified as Predicted epilepsy genes. Finally, 86 genes were identified to be epilepsy genes that were found in all three genetic databases and represent the highest confidence in association with epilepsy. The significance of this study involves the ability to give researchers an up-to-date list of genes that have an association to epilepsy and a summary of information about said genes.

OBJECTIVE:Knowledge about multimorbidity and types of multiple chronic conditions (CC) in people with epilepsy (PWE) seen in an outpatient care setting is lacking. We aim to examine the distribution of multimorbidity and describe the contributing comorbidity of somatic and psychiatric CC in adult PWE in relation to age (≤25; 26-64; ≥65 years), sex (female; male), type of epilepsy (Idiopathic; Structural; Developmental & Epileptic Encephalopathy [DEE]), resistance to treatment (yes; no), and duration of epilepsy (as per 4 quartiles). METHODS:In this observational retrospective cohort study, we assessed 330 adult PWE seen in an epilepsy outpatient clinic. The prevalence of multimorbidity was estimated according to the presence of one or more somatic or psychiatric comorbid CC. We estimated the multimorbidity prevalence within each group and assessed for statistically significant differences. RESULTS:Nearly 80% of PWE seen in an outpatient setting were multimorbid. Over two thirds of participants had a somatic CC and over two fifths a psychiatric CC. These conditions did not occur randomly but varied in relation to age, type of epilepsy, and resistance to treatment. Almost all older adults with epilepsy were multimorbid due to common somatic CC. Neurodevelopmental disorders were often seen in the young adults with epilepsy, people with drug-resistant epilepsy, and/or DEE. The most common chronic comorbid conditions in PWE included depression, anxiety, and insomnia. There appeared to be no influence on the prevalence of multimorbidity in epilepsy based on sex, drug resistance, or duration of epilepsy. CONCLUSION:This is the first study of multimorbidity in adult PWE seen in an outpatient setting and its distribution according to patient and epilepsy characteristics. The findings provide insights into the burden of chronic disease in PWE seen in tertiary care and call for adequate identification and response to patient's needs by health professionals.

Objective The drivers of chronic disease in people with epilepsy with epilepsy (PWE) are unknown. We aimed to identify the role of health risk factors, polypharmacy, and medication usage in (PWE) according to age, sex, epilepsy types, epilepsy duration and resistance to treatment and their relevance to multimorbidity in epilepsy. Methods We analysed patient data from 330 PWE seen in a tertiary centre epilepsy clinic in Perth, Western Australia. The prevalence of biomedical and behavioural health risk factors (including hypertension, obesity or alcohol excess), polypharmacy, antiseizure (ASM) and general medication usage and their association with multimorbidity was investigated, as well as differences that existed across different age groups, sex, epilepsy types, epilepsy duration and resistance to treatment. Results Participants who had ≥1 health risk factor (37 % of participants) had a significantly greater number of comorbidities (p = 0.0008). The number of ASMs and general medications used were positively correlated with the number of comorbidities (p’s < 0.0001). Health risk factors were more commonly present in men (p = 0.0023), at older age (p < 0.0001) and in those with structural epilepsy (p = 0.0002). Polypharmacy was seen in 33 % of participants and was more commonly present in those of older age (p = 0.0003), in developmental and/or epileptic encephalopathy (DEE) (p = 0.0002) and in those with drug-resistant epilepsy (DRE) (p = 00006). Conclusions These findings indicate that health risk factors, polypharmacy and ASM usage are associated with chronic disease and multimorbidity in epilepsy. Routine screening and management of modifiable health risk factors and polypharmacy may reduce the chronic disease burden in PWE and its consequences.

Multimorbidity is an emerging priority in healthcare due to associations with the ageing population, frailty, polypharmacy, health and social care demands. It affects 60-70% of adults and 80% of children with epilepsy. Neurodevelopmental conditions are commonly seen in children with epilepsy, while cancer, cardiovascular and neurodegenerative conditions often afflict older people with epilepsy. Mental health problems are common across the lifespan. Genetic, environmental, social and lifestyle factors contribute to multimorbidity and its consequences. Multimorbid people with epilepsy (PWE) are at higher risk of depression and suicide, premature death, suffer lower health-related quality of life, and require more hospital admissions and health care costs. The best management of multimorbid PWE requires a paradigm shift from the traditional single disease-single comorbidity approach and a refocus on a person-centred approach. Improvements in health care must be informed by assessing the burden of multimorbidity associated with epilepsy, delineating disease clusters, and measuring the effects on health outcomes.

A 39-year-old healthy man presented with stereotyped episodes in sleep since childhood characterized by rhythmic, side-to-side head and body rolling without recollection, injury, or other symptoms. The episodes occurred almost daily, were of variable duration and intensity (3 seconds–3 minutes), and were distressing for his bed partner. There was no daytime sleepiness, and neurologic and physical examination were unremarkable. A 24-hour video-EEG captured events in non-REM and REM sleep (figure; videos 1 and 2 on the Neurology® Web site at Neurology.org), consistent with rhythmic movement disorder, a parasomnia that can also present as head banging or body rocking. Clonazepam1 1 mg nocte was tried for 1 month without effect.

A 31-year-old man presented with a 3-month history of progressive dysarthria and 1 month of gradually worsening motor seizures predominantly affecting the right face. Examination was unremarkable except for a mild spastic dysarthria and slow, alternating tongue movements, probably due to a partial opercular syndrome. Seizures captured during EEG recording showed a jacksonian march starting over the opercular aspect of the motor homunculus,1,2 and anarthria and sialorrhea without EEG correlate (videos 1 and 2 on the Neurology ® Web site at Neurology.org and figure 1). MRI brain showed a left opercular tumor (figure 2, A and B), found to be an anaplastic astrocytoma after resection. The patient has been seizure free for 12 months after treatment with carbamazepine and resective surgery but has residual dysarthria.

Editors' Note: In reference to “Postictal generalized EEG suppression: An inconsistent finding in people with multiple seizures,” Dr. Sethi draws attention to the likely multifactorial relationship between postictal generalized EEG suppression and sudden unexpected death in epilepsy. Authors Lamberts et al. respond. Drs. Lemmer et al. and authors Shellhaas and Barks discuss how the particular model of regional cerebral saturation sensor can affect the data obtained. —Megan Alcauskas, MD, and Robert C. Griggs, MD Lamberts et al. …

PURPOSE:There has been little research on the accessibility and quality of primary care services for epilepsy and emergency hospital admissions for epilepsy. METHODS:We examined time trends in admissions for epilepsy in England between 2004-2005 and 2010, and the association of admission rates with population and primary care factors. The units of analysis were the registered populations of 8622 general practices. We used negative binomial regression to model indicators from the Quality and Outcomes Framework, the UK's primary care pay for performance scheme, to measure the accessibility and quality of care for epilepsy, and supply of general practitioners, after adjustment for population factors. RESULTS:The mean indirectly standardised admission rate decreased from 122.9 to 102.6 (-16.5%; P<0.001) over the study period, while the mean percentage of patients seizure free increased from 65.3% to 74.9% (P<0.001). In the multivariable analysis, a one unit increase in the percentage of seizure free adult patients on epilepsy drugs predicted a 0.20% decrease (IRR=0.9980; 95% CI: 0.9974-0.9986) in admission rate. The percentage of patients who were able to book a GP appointment over two days ahead predicted a 0.12% decrease (IRR=0.9988; 95% CI: 0.9982-0.9994). The deprivation score of practice populations (IRR=1.0179; P<0.001) and general practitioner supply (IRR=1.0022; P<0.001) were both positively associated with admission rates. CONCLUSION:Patient access to primary care appointments and percentage of patients who have been recorded as seizure free for 12 months were associated with lower admission rates. However the effect sizes are small relative to that of population deprivation.

Objective: To determine the consistency and facilitating cofactors of postictal generalized EEG suppression (PGES) of >20 seconds after convulsive seizures (CS), a suggested predictor of sudden unexpected death in epilepsy risk. Methods: We retrospectively reviewed video-EEG data of people with ≥2 recorded CS. Presence and duration of PGES were assessed by 2 independent observers blinded to patient status. Intraindividual consistency of PGES >20 seconds was determined and correlations with clinical characteristics were analyzed after correction for individual effects and the varying number of seizures. Results: One hundred fifty-four seizures in 59 people were analyzed. PGES >20 seconds was found in 37 individuals (63%) and 57 (37%) of CS. The proportion of persons in whom PGES occurred consistently (presence or absence of PGES >20 seconds in all CS) was lower in those with more CS. PGES of >20 seconds was more frequent in seizures arising from sleep (odds ratio 3.29, 95% confidence interval 1.21–8.96) and when antiepileptic medication was tapered (odds ratio 4.80, 95% confidence interval 1.27–18.14). Conclusion: Apparent PGES consistency was less frequent in people with more CS recorded, suggesting that PGES is an inconsistent finding in any one individual. Thus, we believe that PGES >20 seconds is not a reliable predictor of sudden unexpected death in epilepsy. Sleep and antiepileptic drug reduction appear to facilitate the occurrence of PGES.

Background Many physicians request EEG in order to differentiate between syncope and seizure in individuals presenting with transient loss of consciousness (TLOC). This is particularly the case in people taken to hospital following a collapse, where a witness account is not always available. Purpose We aim to investigate the usefulness of EEG in the assessment of unexplained TLOC in a large, unselected group of patients presenting in an emergency department. We also assess the risk of seizure development and clinical course following initial presentation. Methods We retrospectively reviewed referral forms of all routine and urgent EEGs performed at Sir Charles Gairdner Hospital, Perth, Western Australia between April 2010 to November 2011 to identify recordings performed for the investigation of suspected syncope or TLOC. Cases with identifiable cause at initial assessment, and cases suggestive of seizure, previous diagnosis of epilepsy and falls without loss of consciousness were excluded. Diagnosis at discharge and EEG reports were obtained through electronic patient records, EEG archive, and case notes as required. EEGs were classified as normal, abnormal (non–epileptiform abnormalities only), and showing definite epileptiform discharges (EDs). Detailed clinical information including subsequent development of seizures or death was collected for a subgroup of patients with 1–year follow–up after first presentation across all hospitals in the greater Perth area through health electronic linkage. General practitioners and patients were also contacted in order to obtain additional information as needed. The death rate and standardised mortality ratio (SMR) were calculated according to standard methods based on life table 2008–2010 of the Australian Bureau of Statistics. Results We identified 197 cases with unexplained TLOC (age range 18–98 years). No further clinical information was available for 11 cases. The EEG was abnormal in 1/3 of all cases, and in 50% of those over 65 years. EDs were identified in 2 patients (1%); of those, a diagnosis of seizure was made in one patient who was subsequently started on antiepileptic treatment, with no final diagnosis made in the other. Diagnosis at discharge was made in 129 cases (65%) with 23 (18%) of those receiving a seizure diagnosis. The 1–year follow up group consisted of 82 patients (age range 20–95 years); 52 (63%) people were multimorbid (defined as having ≥2 conditions). None of the patients without a seizure diagnosis presented with seizures during follow–up. During this period there were 11 deaths (age range 30–94 years), all in multimorbid people, and none in people with seizure diagnosis. The case fatality rate was 13.4% and SMR 4.27 (95% Fisher9s exact CI, 2.13–7.42). Discussion This study demonstrates that the EEG has a very low diagnostic yield in patients presenting with unexplained TLOC. EEG was helpful in diagnosis of 1 of 2 cases, while a seizure diagnosis was made on clinical grounds in 22 of 23 cases. The high mortality associated with TLOC almost exclusively affected multimorbid patients above 65 years, suggesting high risk of death from an underlying medical cause and not from seizures in this group of patients.

Antiepileptic drugs (AEDs) are used by millions of people worldwide for the treatment of epilepsy, as well as in many other neurological and psychiatric conditions. They are frequently associated with adverse effects (AEs), which have an impact on the tolerability and success of treatment. Half the people who develop intolerable AEs discontinue treatment early on after initiation, while the majority of people will continue to be exposed to their effects for long periods of time. The long-term safety of AEDs reflects their potential for chronic, cumulative dose effects; rare, but potentially serious late idiosyncratic effects; late, dose-related effects; and delayed, teratogenic or neurodevelopmental effects. These AEs can affect every body system and are usually insidious. With the exception of delayed effects, most other late or chronic AEs are reversible. To date, there is no clear evidence of a carcinogenic effect of AEDs in humans. While physicians are aware of the long-term AEs of old AEDs (the traditional liver enzyme-inducing AEDs and valproate), information about AEs of new AEDs (such as lamotrigine, levetiracetam, oxcarbazepine, topiramate or zonisamide), particularly of their teratogenic effects, has emerged over the years. Sporadic publications have raised issues about AEs of the newer AEDs eslicarbazepine, retigabine, rufinamide, lacosamide and perampanel but their long-term safety profiles may take years to be fully appreciated. Physicians should not only be aware of the late and chronic AEs of AEDs but should systematically enquire and screen for these according to the individual AED AE profile. Care should be taken for individuals with comorbid conditions that may render them more susceptible to specific AEs. Prevention and appropriate management of long-term AED AEs is expected to improve adherence to treatment, quality of life and control of epilepsy.

A range of medical and neurologic disorders occurs more frequently in people with epilepsy than in the general population and constitutes its somatic comorbidity. Common examples include cardiac, gastrointestinal, and respiratory disorders; stroke; dementia; and migraine. Alzheimer's disease and migraine are not only more common in epilepsy but are also risk factors for the development of seizures, suggesting a bidirectional association and shared disease mechanisms. Less well-appreciated associations with epilepsy include Parkinson's disease and obstructive sleep apnea. The association between epilepsy and other conditions can be due to a variety of interacting genetic, biologic, and environmental factors. We propose an etiologic classification of comorbidity into uncertain (coincidence or unknown), causal (cause), shared risk factors (common disease mechanisms or shared predisposing risk factors), and resultant (consequence). Co-occurrence of other conditions in a person with epilepsy can complicate diagnosis or have adverse prognostic implications. Management of these conditions may facilitate the treatment of epilepsy, as in the case of obstructive sleep apnea. The presence of somatic disorders in epilepsy is associated with increased health care needs, poorer health-related quality of life, and premature mortality. Prevention, identification, and adequate treatment of comorbid disorders in epilepsy should be an important part of epilepsy management at all levels of care.

Introduction:Syncope is a common presenting complaint in Neurology clinics or Emergency departments, but its causes are sometimes difficult to diagnose. Apart from vasovagal attacks, other benign, neurally mediated syncopes include “situational” syncopes, which occur after urination, coughing, swallowing, or defecation. Case Report:A healthy 42-year-old male patient presented to the neurology clinic with a long history of faints triggered by spontaneous laughter, especially after funny jokes. Physical and neurological examination, and electroencephalography and magnetic resonance imaging were unremarkable. There was no evidence to suggest cardiogenic causes, epilepsy, or cataplexy and a diagnosis of laughing syncope was made. Conclusions:Laughter-induced syncope is usually a single event in the majority of cases, but may present as recurrent attacks as in our case. Some cases occur in association with underlying neurological conditions. Prognosis is good in the case of neurally mediated attacks. Laughter may not be recognized by physicians as a cause of syncope, which may lead to unnecessary investigations or misdiagnosis, and affect patients’ quality of life.