Emotional and Behavioral Problems in Children with Epilepsy Attending the Pediatric Neurology Clinic at a Referral Hospital in Kenya

Abstract, originally published in Epilepsy & Behavior

Introduction: Epilepsy is a common neurological condition, with a lifetime prevalence of 1% in children. Research has shown a high prevalence of emotional and behavioral problems in children with epilepsy. The aim of this study was to determine the prevalence of emotional and behavioral problems in children with epilepsy attending the pediatric neurology clinic in a referral hospital in Kenya and examine associated sociodemographic and clinical variables.

Methods: This was a cross-sectional descriptive study. Children with epilepsy aged between 6 and 12 years attending the Kenyatta National Hospital pediatric neurology clinic were recruited. Inclusion criteria for the study were children diagnosed with epilepsy, age between 6 and 12 years, accompanied by a primary caregiver, and the primary caregiver being willing to participate in the study. A sociodemographic questionnaire as well as the Child Behavior Checklist school-age version (CBCL/6-18) was administered to the caregiver accompanying the child.

Results: One hundred and seventy-seven children with epilepsy were recruited (66% males) with a mean age of 8.9 (standard deviation (SD): 2) years. The mean age at onset of seizures was 4.5 years; 48% of the children had first seizure while aged less than 2 years, 76% reported generalized tonic-clonic seizures, and 58% were on antiepileptic drugs (AEDs). The overall prevalence of emotional and behavioral problems was 46%, and the four leading symptom clusters were attention problems, aggressive behavior, social problems, and withdrawal/depression. The risk of emotional and behavioral problems was increased in children using more than one AED (odds ratio (OR) = 2.21, 95% confidence interval (CI), 1.18-4.14) and those aged ten years and above (OR = 2.7, 95% CI, 1.3-5.64). The risk of emotional and behavioral problems was reduced in children with infrequent seizures (OR = 0.08, 95% CI, 0.01-0.06) and in children reporting no seizure in the past year (OR = 0.08, 95% CI, 0.01-0.65).

Conclusion: Emotional and behavioral problems are common among children with epilepsy in Kenya. This highlights the need to screen for these problems in children on treatment for epilepsy for early identification and subsequent management to improve outcome.

Predicting epilepsy from neural network models

Summary, originally published in European Physical Journal B

Within the staggeringly complex networks of neurons which make up our brains, electric currents display intricate dynamics in the electric currents they convey. To better understand how these networks behave, researchers in the past have developed models which aim to mimic their dynamics. In some rare circumstances, their results have indicated that ‘tipping points’ can occur, where the systems abruptly transition from one state to another: events now commonly thought to be associated with episodes of epilepsy. In a new study published in EPJ B, researchers led by Fahimeh Nazarimehr at the University of Technology, Tehran, Iran, show how these dangerous events can be better predicted by accounting for branches in networks of neurons.

The team’s findings could give researchers a better understanding of suddenly occurring episodes including epilepsy and asthma attacks, and may enable them to develop better early warning systems for patients who suffer from them. To do this, the study considered how the dynamics of neuron activity are influenced by branches in the networks they form. Previous models have shown that these dynamics will often slow down at these points — yet so far, they have been unable to predict how the process unfolds in larger, more complex networks of neurons.

Nazarimehr’s team improved on these techniques using updated models, where the degree to which adjacent neurons influence each other’s dynamics can be manually adjusted. In addition, they considered how the dynamics of complex neuron networks compare with those of isolated cells. Together, these techniques enabled the researchers to better predict where branching occurs; and subsequently, how the network’s dynamics are affected. Their results represent an advance in our understanding of the brain’s intricate structure, and how the dynamics of the electric currents it contains can be directly related to instances of epilepsy.

FBXO28 causes developmental and epileptic encephalopathy with profound intellectual disability

Abstract, originally published in Epilepsia

Chromosome 1q41-q42 deletion syndrome is a rare cause of intellectual disability, seizures, dysmorphology, and multiple anomalies. Two genes in the 1q41-q42 microdeletion, WDR26 and FBXO28, have been implicated in monogenic disease. Patients with WDR26 encephalopathy overlap clinically with those with 1q41-q42 deletion syndrome, whereas only one patient with FBXO28 encephalopathy has been described. Seizures are a prominent feature of 1q41-q42 deletion syndrome; therefore, we hypothesized that pathogenic FBXO28 variants cause developmental and epileptic encephalopathies (DEEs). We describe nine new patients with FBXO28 pathogenic variants (four missense, including one recurrent, three nonsense, and one frameshift) and analyze all 10 known cases to delineate the phenotypic spectrum. All patients had epilepsy and 9 of 10 had DEE, including infantile spasms (3) and a progressive myoclonic epilepsy (1). Median age at seizure onset was 22.5 months (range 8 months to 5 years). Nine of 10 patients had intellectual disability, which was profound in six of nine and severe in three of nine. Movement disorders occurred in eight of 10 patients, six of 10 had hypotonia, four of 10 had acquired microcephaly, and five of 10 had dysmorphic features, albeit different to those typically seen in 1q41-q42 deletion syndrome and WDR26 encephalopathy. We distinguish FBXO28 encephalopathy from both of these disorders with more severe intellectual impairment, drug-resistant epilepsy, and hyperkinetic movement disorders.

Managing Depression and Anxiety in People with Epilepsy: A Survey of Epilepsy Health Professionals by The ILAE Psychology Task Force

Abstract, originally published in Epilepsia Open

Objectives: The Psychology Task Force of the Medical Therapies Commission of the International League Against Epilepsy (ILAE) has been charged with taking steps to improve global mental health care for people with epilepsy. This study aimed to inform the direction and priorities of the Task Force by examining epilepsy health care providers’ current practical experiences, barriers and unmet needs around addressing depression and anxiety in their patients.

Methods: A voluntary 27-item online survey was distributed via ILAE chapters and networks. It assessed practices in the areas of screening, referral, management and psychological care for depression and anxiety. A total of 445 participants, from 67 countries (68% high income), commenced the survey, with 87% completing all components. Most respondents (80%) were either neurologists or epileptologists.

Results: Less than half of respondents felt adequately resourced to manage depression and anxiety. There was a lack of consensus about which health professionals were responsible for screening and management of these comorbidities. About a third only assessed for depression and anxiety following spontaneous report and lack of time was a common barrier (>50%). Routine referrals to psychiatrists (>55%) and psychologists (>41%) were common, but approximately one third relied on watchful waiting. A lack of both trained mental health specialists (>55%) and standardized procedures (>38%) were common barriers to referral practices. The majority (>75%) of respondents’ patients identified with depression or anxiety had previously accessed psychotropic medications or psychological treatments. However, multiple barriers to psychological treatments were endorsed, including accessibility difficulties (52%).

Significance: The findings suggest that while the importance of managing depression and anxiety in patients with epilepsy is being recognized, there are ongoing barriers to effective mental health care. Key future directions include the need for updated protocols in this area and the integration of mental health professionals within epilepsy settings.

People With Epilepsy at Slightly Increased Risk of More Severe COVID-19 Symptoms, Study Suggests

Abstract, originally published in Epilepsy Today

There is a slightly increased risk of hospital admission and death from COVID-19 in people with epilepsy, according to a new study in the British Medical Journal (BMJ).

The research, published in October 2020, looked at risk factors for hospital admissions and death from COVID-19 in 6.08 million adults across England. The data were collected between January 24 and April 30.

Among the risk factors were conditions for which people are advised to shield, and conditions moderately associated with increased risk of complications from COVID-19, according to current NHS guidance.

The evidence from the research by Clift and colleagues showed a small increase in risk of hospital admissions and deaths resulting from COVID-19 in both men and women with epilepsy. The risk appears to be slightly higher still in men than in women.

Among the highest risk factors were conditions like Down’s syndrome and sickle cell disease or severe immunodeficiency, as well as treatments like higher grade chemotherapy.

Translation and Validation of an Epilepsy-Screening Questionnaire in Three Nigerian Languages

Abstract, published in Epilepsy & Behavior

Objective: We describe the development, translation and validation of epilepsy-screening questionnaires in the three most popular Nigerian languages: Hausa, Igbo and Yoruba.

Methods: A 9-item epilepsy-screening questionnaire was developed by modifying previously validated English language questionnaires. Separate multilingual experts forward- and back-translated them to the three target languages. Translations were discussed with fieldworkers and community members for ethnolinguistic acceptability and comprehension. We used an unmatched affected-case versus unaffected-control design for the pilot study. Cases were people with epilepsy attending the tertiary hospitals where these languages are spoken. The controls were relatives of cases or people attending for other medical conditions. An affirmative response to any of the nine questions amounted to a positive screen for epilepsy.

Results: We recruited 153 (75 cases and 78 controls) people for the Hausa version, 106 (45 cases and 61 controls) for Igbo and 153 (66 cases and 87 controls) for the Yoruba. The sensitivity and specificity of the questionnaire were: Hausa (97.3% and 88.5%), Igbo (91.1% and 88.5%) and Yoruba (93.9% and 86.7%). The three versions reliably indicated epilepsy with positive predictive values of 85.9% (Hausa), 85.4% (Igbo) and 87.3% (Yoruba) and reliably excluded epilepsy with negative predictive values of 97.1% (Hausa), 93.1% (Igbo) and 95.1% (Yoruba). Positive likelihood ratios were all greater than one.

Conclusions: Validated epilepsy screening questionnaires are now available for the three languages to be used for community-based epilepsy survey in Nigeria. The translation and validation process are discussed to facilitate usage and development for other languages in sub-Saharan Africa.

Economic Burden of Epilepsy in Children: A Population-Based Matched Cohort Study in Canada

Abstract, originally published in Epilepsia

Objective: The economic burden of childhood epilepsy to the health care system remains poorly understood. This study aimed to determine phase-specific and cumulative long-term health care costs in children with epilepsy (CWE) from the health care payer perspective.

Methods: This cohort study utilized linked health administrative databases in Ontario, Canada. Incident childhood epilepsy cases were identified from January 1, 2003 to June 30, 2017. CWE were matched to children without epilepsy (CWOE) on age, sex, rurality, socioeconomic status, and comorbidities, and assigned prediagnosis, initial, ongoing, and final care phase based on clinical trajectory. Phase-specific, 1-year and 5-year cumulative health care costs, attributable costs of epilepsy, and distribution of costs across different ages were evaluated.

Results: A total of 24 411 CWE were matched to CWOE. The costs were higher for prediagnosis and initial care than ongoing care in CWE. Hospitalization was the main cost component. The costs of prediagnosis, initial, and ongoing care were higher in CWE than CWOE, with the attributable costs at $490 (95% confidence interval [CI] = $352-$616), $1322 (95% CI = $1247-$1402), and $305 (95% CI = $276-$333) per 30 patient-days, respectively. Final care costs were lower in CWE than CWOE, with attributable costs at —$2515 (95% CI = —$6288 to $961) per 30 patient-days. One-year and 5-year cumulative costs were higher in CWE ($14 776 [95% CI = $13 994-$15 546] and $39 261 [95% CI = $37 132-$41 293], respectively) than CWOE ($6152 [95% CI = $5587-$6768] and $15 598 [95% CI = $14 291-$17 006], respectively). The total health care costs were highest in the first year of life in CWE for prediagnosis, initial, and ongoing care.

Significance: Health care costs varied along the continuum of epilepsy care, and were mainly driven by hospitalization costs. The findings identified avenues for remediation, such as enhancing care around the time of epilepsy diagnosis and better care coordination for epilepsy and comorbidities, to reduce hospitalization costs and the economic burden of epilepsy care.

Seizure Control, Stress, and Access to Care During the COVID-19 Pandemic in New York City: The Patient Perspective

Abstract, originally published in Epilepsia

Objective: Our epilepsy population recently experienced the acute effects of the COVID-19 pandemic in New York City. Herein, we aimed to determine patient-perceived seizure control during the surge, specific variables associated with worsened seizures, the prevalence of specific barriers to care, and patient-perceived efficacy of epilepsy care delivered via telephone and live video visits during the pandemic.

Methods: We performed a cross-sectional questionnaire study of adult epilepsy patients who had a scheduled appointment at a single urban Comprehensive Epilepsy Center (Montefiore Medical Center) between March 1, 2020 and May 31, 2020 during the peak of the COVID-19 pandemic in the Bronx. Subjects able to answer the questionnaire themselves in English or Spanish were eligible to complete a one-time survey via telephone or secure online platform (REDCap).

Results: Of 1212 subjects screened, 675 were eligible, and 177 adequately completed the questionnaire. During the COVID-19 pandemic, 75.1% of patients reported no change in seizure control, whereas 17.5% reported that their seizure control had worsened, and 7.3% reported improvement. Subjects who reported worsened seizure control had more frequent seizures at baseline, were more likely to identify stress and headaches/migraines as their typical seizure precipitants, and were significantly more likely to report increased stress related to the pandemic. Subjects with confirmed or suspected COVID-19 did not report worsened seizure control. Nearly 17% of subjects reported poorer epilepsy care, and 9.6% had difficulty obtaining their antiseizure medications; these subjects were significantly more likely to report worse seizure control.

Significance: Of the nearly 20% of subjects who reported worsened seizure control during the COVID-19 pandemic, stress and barriers to care appear to have posed the greatest challenge. This unprecedented pandemic exacerbated existing and created new barriers to epilepsy care, which must be addressed.

Stress increases susceptibility to pentylenetetrazole-induced seizures in adult zebrafish

Abstract, originally published in Epilepsy & Behavior

Stress is the body’s reaction to any change that requires adaptive responses. In various organisms, stress is a seizure-related comorbidity. Despite the exposure to stressors eliciting aversive behaviors in zebrafish, there are no data showing whether stress potentiates epileptic seizures in this species.

Here, we investigated whether a previous exposure to an intense acute stressor positively modulates the susceptibility to seizures in pentylenetetrazole (PTZ)-challenged zebrafish.

The conspecific alarm substance (CAS) was used to elicit aversive responses (3.5 mL/L for 5 min), observed by increased bottom dwelling and erratic movements. Then, fish were immediately exposed to 7.5 mM PTZ for 10 min to induce seizure-like behaviors. Stress increased the seizure intensity, the number of clonic-like seizure behaviors (score 4), as well as facilitated the occurrence of score 4 episodes by decreasing the latency in which fish reached the score 4. Moreover, fish with heightened anxiety showed increased susceptibility to PTZ, since positive correlations between anxiety- and seizure-like behaviors were found. Overall, since CAS also increased whole-body cortisol levels in zebra fish, our novel findings show a prominent response to PTZ-induced seizures in previously stressed zebrafish. Moreover, we reinforce the growing utility of zebrafish models to assess seizure-related comorbidities aiming to elucidate how stress can affect epileptic seizures in vertebrates.

Would people living with epilepsy benefit from palliative care?

Abstract, originally published in Epilepsy & Behavior

Palliative care (PC) is an approach to the care of persons living with serious illness and their families that focuses on improving quality of life and reducing suffering by addressing complex medical symptoms, psychosocial needs, spiritual well-being, and advance care planning. While PC has traditionally been associated with hospice care for persons with cancer, there is now recognition that PC is relevant to many noncancer diagnoses, including neurologic illness, and at multiple points along the illness journey, not just end of life.

Despite the recent growth of the field of neuropalliative care there has been scant attention paid to the relevance of PC principles in epilepsy or the potential for PC approaches to improve outcomes for persons living with epilepsy and their families. We believe this has been a significant oversight and that PC may provide a useful framework for addressing the many sources of suffering facing persons living with epilepsy, for engaging patients and families in challenging conversations, and to focus efforts to improve models of care for this population.

In this manuscript we review areas of significant unmet needs where a PC approach may improve patient and family-centered outcomes, including complex symptom management, goals of care, advance care planning, psychosocial support for patient and family and spiritual well-being. When relevant we highlight areas where epilepsy patients may have unique PC needs compared to other patient populations and conclude with suggestions for future research, clinical, and educational efforts.