How much do children with disabilities participate in Clinical Trials? A Scoping review.

BACKGROUND: Children with disabilities (CWDs) are often excluded from scientific research, but no precise data are available on their participation in Clinical Trials. The aim of this study was to evaluate the rates of exclusion of CWDs from recent medical research. SUBJECTS AND METHODS: The protocol of the study was designed according to Prisma-ScR guidelines. All completed interventional Clinical Trials registered on Clinicaltrials.gov between 2010 and 2020 related to the Leading 10 Level 3 causes of global Disability-adjusted life years (DALYs) for both sexes combined for all ages of the updated Global Burden of Disease Study 2019 were analysed. The exclusion criteria were considered explicit if related to the following categories: disability, physical impairment, cognitive impairment, behavioural or psychiatric disorders, language and communication impairment, sensory impairment. Any generic or poorly specified exclusion criteria or statements that left wide discretion to researchers were considered "implicit exclusion criteria". We assessed the appropriateness of explicit exclusion criteria in relation to the primary objectives of the trials and labelled them as "absolute", "relative", or "questionable". RESULTS: The trials selected according to the inclusion criteria of the scoping review were 328; 166 (50.6%) were pediatric-only studies, and 162 (49.4%) trials comprising subjects of all ages. Explicit exclusion criteria were found in 82 trials (25%) and the disability category most frequently excluded was "Behavioural or psychiatric disorders" present in 46 trials (56.1%). Explicit exclusion criteria were considered "relative" in over 90% of the selected studies. Implicit exclusion criteria were present in 153 trials (46.6%) and the number and percentage of studies with at least one explicit or implicit exclusion criterion were 193 and 58.8% respectively. CONCLUSIONS: This study highlights a high rate of exclusion of CWDs from medical research and the need for an inclusive approach that comprises the study design and any necessary adaptations for specific needs.

Pain Assessment in People with Intellectual Disability: Improving Skills of Health and Educational Personnel at Istituto Serafico of Assisi, Italy.

BACKGROUND: Assessment of pain in people with intellectual disability (PWID) is a difficult clinical task. Poor knowledge and confidence in assessing pain in PWID result in underestimation and undertreatment. Available resources for healthcare personnel and caregivers on pain assessment in PWID are still very limited. The aim of the study was to measure the level of knowledge and confidence in assessing pain in PWID of health and education personnel at Istituto Serafico, before and after training. SUBJECTS AND METHODS: The Istituto Serafico is a neuro-rehabilitation center caring for people with complex disabilities. Nurses, rehabilitation therapists, social health workers (SHW) and educators were invited to participate in a 4-hours theoretical and practical training. Participants were assessed through a knowledge and confidence questionnaire on pain assessment in PWID, administered before and after the training. RESULTS: 123 participants attended both the theoretical and practical sessions. Median age was 43 years (range 23-67); 89 were females and 34 males. They were 10 (8%) nurses, 9 (7%) rehabilitation therapists, 77 (63%) SHW, 27 (22%) educators. Only 7 (6%) participants (5 nurses and 2 SHW) declared to have previously received formation on pain. Participants who felt "quite confident" in assessing pain increased from 28% to 73% after the training. The median score to the 24 knowledge questions raised from 15/24 correct answers (range 6-22, 62.5%) in the pre-test to 21/24 (range 11-24, 87.5%) in the post-tests (p=0.001) Conclusions: The study highlights the great need of education programs for health and educational personnel working with PWID on pain assessment and the potential to improve knowledge and confidence through theoretical and practical training. A greater awareness of pain causes, clinical manifestations and consequences of untreated pain, could improve patient care, quality of life and rehabilitation goals.

'Being disabled' as an exclusion criterion for clinical trials: a scoping review.

BACKGROUND: People with disabilities (PWDs) are often excluded from biomedical research, but comprehensive data regarding their participation in clinical trials are not available. The objective of this study was to assess the rates of exclusion of PWDs from recent medical scientific research. METHODS: The protocol of the study was designed according to PRISMA-ScR (PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) extension for Scoping Reviews) guidelines. All completed interventional clinical trials registered on ClinicalTrials.gov between 2010 and 2020 regarding the 10 leading causes of global disability-adjusted life-years according to the Global Burden of Disease Study were analysed. An exclusion criterion from the study was considered explicit if it could be associated with one of the following seven categories: disability, physical impairment, cognitive impairment, behavioural or psychiatric disorders, language and communication impairment, sensory impairment. Comorbidities not more clearly defined and researcher discretion regarding exclusion of study participants were considered to be 'implicit exclusion criteria'. We assessed the appropriateness of explicit exclusion criteria in relation to the primary objectives of the trials and labelled them as 'absolute', 'relative' or 'questionable'. RESULTS: The total number of trials analysed was 2710; 170 were paediatric trials (6.3%), 2374 were adult trials (87.6%) and 166 were trials including subjects of all ages (6.1%). Explicit exclusion criteria were found in 958 trials (35.3%). The disability category most frequently excluded was behavioural or psychiatric disorders, present in 588 trials (61.4%). In only 3% and 1% of the trials, the exclusion criteria were considered either 'absolute' or 'questionable', while in 96% the exclusion criteria were judged as 'relative'. Implicit exclusion criteria were present in 1205 trials (44.5%). CONCLUSIONS: This study highlights the high rate of exclusion of PWDs from biomedical research and the widespread use of ill-defined exclusion criteria in clinical trials. It underscores the importance of more inclusive study designs so that PWDs can become active participants in research.

The prevalence of primary headache disorders in children and adolescents in Zambia: a schools-based study.

BACKGROUND: The Global Campaign against Headache collects data from children (6-11 years) and adolescents (12-17) to inform health and education policies and contribute to the Global Burden of Disease (GBD) study. This survey in Zambia, part of this global enquiry, was the second from sub-Saharan Africa (SSA). METHODS: Following the generic protocol, this was a schools-based cross-sectional survey. We used the child and adolescent versions of the structured Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, self-completed by pupils within classes, in a total of nine schools in Lusaka (urban) and Copperbelt (semi-rural). These two of Zambia's ten provinces were selected to represent the country's urban/rural divide. Headache diagnostic questions were based on ICHD-3 except for undifferentiated headache (UdH). RESULTS: Of 2,759 potential participants, 2,089 (615 children [29.4%], 1,474 adolescents [70.6%]) completed questionnaires (participating proportion 75.7%). Children were therefore under-represented (mean age 13.1 ± 2.8 years), while gender distribution (1,128 [54.0%] male, 961 [46.0%] female) was close to expectation. Observed lifetime prevalence of headache was 97.5%. Gender- and age-adjusted 1-year prevalence estimates were 85.8% for all headache, 53.2% for migraine (definite 17.5%, probable 35.7%), 12.1% for tension-type headache (TTH), 14.8% for UdH, 3.3% for all headache on ≥ 15 days/month and 0.9% for probable medication-overuse headache. Headache durations were short: only 28.6% of participants with any headache, and only 10.5% of those diagnosed as probable migraine, reported usual durations of > 2 h (the threshold for definite migraine). Of the latter, 36.6% reported < 1 h, the duration criterion for UdH. There were weak associations of migraine (definite + probable) with female gender, and of TTH and headache on ≥ 15 days/month with adolescence. Headache yesterday was reported by 22.2% of the sample, 25.5% of those with headache. CONCLUSIONS: Headache disorders among young people are prevalent in Zambia. Among them, migraine is the most common, with UdH also highly prevalent. In this study there were diagnostic uncertainties, which rested to a large extent on the distinction between migraine and UdH among the many participants reporting headache of < 2 h' duration. Similar uncertainties occurred in the first study in SSA, in Ethiopia. Because of these, we conclude only that migraine affects at least 17.5% of these age groups in Zambia, which is still a large proportion, adult prevalence in an earlier study being 22.9%. Supplementary estimates of attributed burden are needed to inform public-health and educational policies in Zambia.

Clinical characteristics and outcomes after new-onset seizure among Zambian children with HIV during the antiretroviral therapy era.

OBJECTIVE: This study describes clinical profiles including human immunodeficiency virus (HIV) disease history and seizure etiology among children living with HIV presenting with new-onset seizure during the era of antiretroviral therapy (ART) in Zambia. 30-day mortality and cause of death are also reported. METHODS: Children living with HIV (CLWHIV) with new-onset seizures were prospectively evaluated at one large urban teaching hospital and two non-urban healthcare facilities. Interviews with family members, review of medical records, and where needed, verbal autopsies were undertaken. Two clinicians who were not responsible for the patients' care independently reviewed all records and assigned seizure etiology and cause of death with adjudication as needed. RESULTS: From April 2016 to June 2019, 73 children (49 urban, 24 rural) were identified. Median age was 6 years (IQR 2.2-10.0) and 39 (53%) were male children. Seizures were focal in 36 (49%) and were often severe, with 37% presenting with multiple recurrent seizures in the 24 hours before admission or in status epilepticus. Although 36 (49%) were on ART at enrollment, only 7 of 36 (19%) were virally suppressed. Seizure etiologies were infectious in over half (54%), with HIV encephalitis, bacterial meningitis, and tuberculous meningitis being the most common. Metabolic causes (19%) included renal failure and hypoglycemia. Structural lesions identified on imaging accounted for 10% of etiologies and included stroke and non-accidental trauma. No etiology could be identified in 12 (16%) children, most of whom died before the completion of clinical investigations. Twenty-two (30%) children died within 30 days of the index seizure. SIGNIFICANCE: Despite widespread ART roll out in Zambia, new-onset seizure in CLWHIV occurs in the setting of advanced, active HIV disease. Seizure severity/burden is high as is early mortality. Enhanced programs to assure early ART initiation, improve adherence, and address ART failure are needed to reduce the burden of neurological injury and premature death in CLWHIV.

Survey on the worldwide availability and affordability of antiseizure medications: Report of the ILAE Task Force on Access to Treatment.

Health systems worldwide are challenged in the provision of basic medical services and access to treatments for chronic conditions. Epilepsy, the most common severe chronic neurological disorder, does not receive sufficient attention despite being officially declared a public health priority by the World Health Organization. More than 80% of people with epilepsy live in middle- and low-income countries (MICs and LICs, respectively), where most of the population lacks reliable access to antiseizure medications (ASMs), contributing significantly to the large epilepsy treatment gap in these regions. The International League Against Epilepsy (ILAE) Task Force on Access to Treatment administered a global survey to report on the current access to ASMs worldwide. The survey was developed and distributed online through the ILAE and International Bureau of Epilepsy (IBE) secretariats to the chapter representatives. The survey was completed by one representative per country. Response rate was 73.2% (101 countries of the 138 represented in ILAE and/or IBE organizations). Availability and access of ASMs, including distribution problems and costs, reimbursement procedures, general barriers to access to care, and presence of projects targeted toward improving care access, were studied, and descriptive statistics on available responses were performed. Among the 15 first-generation ASMs surveyed, carbamazepine was reported as the most widely available globally. At least one first-generation ASM is widely available in most countries, but their number differs dramatically across income levels. Second- and third-generation ASMs are even more limited in MICs and LICs. Additionally, average retail prices for ASMs were not significantly different across countries despite the differences in per capita income from high-income countries to LICs. This survey provides a worrisome picture of availability and accessibility of ASMs across the world, with wide disparities according to socioeconomic status. Recommendations for direct action on improving access to care will be discussed.

Intellectual Disability and Psychiatric Disorders as Exclusion Criteria in Randomized Controlled Trials (RCT).

People with intellectual disability or psychiatric disorders are commonly excluded from Randomized Controlled Trials (RCTs) because of explicit exclusion to the trials or because of inaccessible research protocols. We analyzed the exclusion rate of persons with cognitive impairment, psychiatric disorders and inability to give informed consent in interventional RCTs about the first 10 causes of global DALYs (disability- adjusted life-years) according to the Global Burden of Disease Study (GBD) utilizing the website Clinicaltrials.gov. A total of 2809 studies in the 10 selected categories were reviewed. "Cognitive impairment" was present in 488 (17.4%) studies, "Behavioural and psychiatric disorders" was present in 616 (21.9%) studies, "Inability to grant informed consent" was present in 498 (17.7%) studies and the three explicit criteria were present, alone or in combination, in 1076 studies (38.3%). Other disability-related exclusion criteria were considered to be implicit exclusion criteria and were present in 1233 (43.9%) studies. A judgement was made on the correlation between the exclusion criteria and the primary objectives of the studies analyzed. The low level of representation of people with disabilities in RCTs, in addition to being an ethical problem, is a limitation of scientific knowledge because it considerably reduces the external validity of a significant part of medical research. There is a need to review the way scientific research designs are constructed, seeking to promote greater inclusiveness of people with disabilities.

Development and Evaluation of a Pediatric Epilepsy Training Program for First Level Providers in Zambia.

Introduction. The developing world continues to face challenges in closing the large treatment gap for epilepsy, due to a high burden of disease and few experienced providers to manage the condition. Children with epilepsy are susceptible to higher rates of developmental impairments and refractory disease due to delays or absence of appropriate management as a result. We demonstrated that a structured education intervention on pediatric epilepsy can improve knowledge, confidence, and impact clinical practice of first level providers in Zambia. Methods. Three first-level facilities across Zambia were included. After initial pilot versions and revisions, the final course was implemented at each site. Pre- and post-intervention knowledge and confidence assessments were performed. Additionally, chart reviews were conducted prior to intervention and 4 months after completion of training at each site to assess change on management. Results. Twenty-three of the original 24 participants from all 3 sites completed the training; 48% clinical officers, 43% nurses, 9% other expertise. Of the 15 concepts tested by knowledge assessment, 12 showed trends in improvement, 7 of which were significant (P < .05). Chart reviews demonstrated significant improvement in documentation of seizure description (P = .008), seizure frequency (P = .00), and possible causes of seizures/epilepsy (P = .034). Discussion. Key elements of success to this program included hands on clinical skills building and case-based teaching, development of a program with direct and ongoing input from the target audience, and inclusion of assessments to monitor impact on clinical practice. Future studies looking at health outcomes are necessary to determine sustained impact.

Ketogenic diet in Zambia: Managing drug-resistant epilepsy in a low and middle income country.

Globally, drug-resistant epilepsy affects one third of people living with epilepsy. With limitations in treatment options for refractory epilepsy in resource-limited regions, ketogenic diet therapy is an important option to consider. Utilizing the 2015 International League Against Epilepsy recommended minimum requirements for ketogenic diet therapy, three male children with refractory epilepsy, aged 2.5, 6.5 and 10 years, were initiated on the classical ketogenic diet using locally available food in August 2017 at University Teaching Hospitals-Children's Hospital in Lusaka, Zambia, through partnership with the Epilepsy Program at Boston Children's Hospital in the United States. Following successful initiation in all three children, the diet was discontinued in the 10-year-old due to difficulties complying with the diet. The youngest child demonstrated an over 50% seizure reduction and gained developmental milestones. The third child achieved seizure freedom and showed marked improvement in behaviour. This pilot demonstrates the feasibility of ketogenic diet as an important therapeutic option for refractory epilepsy in Zambia. Given the limitations in treatment choices and medication accessibility, dietary therapy offers an alternative management strategy in our setting. Collaboration with an established ketogenic diet centre contributes to a successful program.

Improving paediatric epilepsy management at the first level of care: a pilot education intervention for clinical officers in Zambia.

OBJECTIVE: Epilepsy affects approximately 50 million people globally, with approximately 80% living in low/middle-income countries (LMIC), where access to specialist care is limited. In LMIC, primary health workers provide the majority of epilepsy care, despite limited training in this field. Recognising this knowledge gap among these providers is an essential component for closing the epilepsy treatment gap in these regions. SETTING: In Zambia, the vast majority of healthcare is provided by clinical officers (COs), primary health providers with 3 years post-secondary general medical education, who predominantly work in first-level health centres around the country. PARTICIPANTS: With cooperation from the Ministry of Health, a total of 10 COs from 4 surrounding first-level health centres around the capital city of Lusaka participated, with 9 completing the entire course. INTERVENTION: COs were trained in a 3-week structured course on paediatric seizures and epilepsy, based on adapted evidence-based guidelines. RESULTS: Preassessment and postassessment were conducted to assess the intervention. Following the course, there was improved overall knowledge about epilepsy (69% vs 81%, p<0.05), specifically knowledge regarding medication management and recognition of focal seizures (p<0.05), improved seizure history taking and appropriate medication titration (p<0.05). However, knowledge regarding provoked seizures, use of diagnostic studies and general aetiologies of epilepsy remained limited. CONCLUSIONS: This pilot project demonstrated that a focused paediatric epilepsy training programme for COs can improve knowledge and confidence in management, and as such is a promising step for improving the large epilepsy treatment gap in children in Zambia. With feasibility demonstrated, future projects are needed to expand to more rural regions for more diverse and larger sample of primary health provider participants and encompass more case-based training and repetition of key concepts as well as methods to improve and assess long-term knowledge retention.

A retrospective observational study of EEG findings and antiepileptic drug use among children referred for EEG to Zambia's University Teaching Hospital.

OBJECTIVE: Despite the heavy burden of epilepsy in Sub-Saharan Africa, there remains a relative paucity of neurophysiology services and limited published data on electroencephalography (EEG) features among African children. The aim of this study was to describe clinical characteristics, EEG findings, and antiepileptic drug (AED) use among children referred for EEG to the University Teaching Hospital in Zambia. METHODS: EEG referrals and reports from 2013-2015 were reviewed. Within the context of routine care, EEG studies were interpreted by readers with advanced training in child neurology and clinical neurophysiology. Clinical data provided in the referral including seizure semiology and EEG findings were systematically extracted and analyzed. RESULTS: A total of 1,217 EEG reports were reviewed, with 1,187 included in the analysis. Median age was 7 years (interquartile range [IQR] 3-11) and 57% were male. Seventy-three percent of 554 had documented seizure onset before 5 years of age. Among the 23% with seizure etiology documented, 78% were associated with perinatal injuries and central nervous system (CNS) infections. EEG abnormalities were found in 75% of the studies. Clinical semiology per referral identified focal seizures in 29%, but EEG findings increased this proportion to 63% (p = 0.004). Sixty-two percent were taking AEDs, with 85% on monotherapy. The most commonly used AED was carbamazepine (49%).There was no association between the choice of AED and clinical semiology (all p's > 0.05). SIGNIFICANCE: This tertiary care center study identified >60% of referred children to have localization-related epilepsies, with at least 18% of epilepsies being from potentially preventable causes. These findings are consistent with multi-country, population-based data from elsewhere in Africa. Seizure semiology assessed in routine, nonspecialist care does not predict AED choice, and the presence of focality is underestimated in routine care.

Children infected by human herpesvirus 6B with febrile seizures are more likely to develop febrile status epilepticus: A case-control study in a referral hospital in Zambia.

BACKGROUND: Human herpesvirus 6B (HHV-6B) is the causative agent of Roseola infantum, and has also been suggested to play a role in the pathogenesis of febrile seizures in young children, a percentage of whom go on to develop febrile status epilepticus (FSE), but the existing data is conflicting and inconclusive. HHV-6A is a distinct species, rarely detected in most parts of the world, but prior studies suggest a higher prevalence in febrile African children. We describe a case-control study comparing the frequency of HHV-6A and/or HHV-6B infections in children with febrile seizures (including FSE) and a control group of febrile children without seizures. METHODS: We recruited children aged 6 to 60 months admitted with a febrile illness with (cases) or without (controls) seizures presenting within 48 hours of commencement of fever. Three milliliters of whole blood was centrifuged and plasma stored at -80°C for pooled screening for HHV-6B and HHV-6A by Taqman real-time polymerase chain reaction. RESULTS: 102 cases and 95 controls were recruited. The prevalence of HHV-6B DNA detection did not differ significantly between cases (5.8% (6/102)) and controls (10.5% (10/95)) but HHV-6B infection was associated with FSE (OR, 15; 95% CI, [1.99-120]; P= 0.009). HHV-6A was not detected. CONCLUSION: Prevalence of HHV-6B was similar among cases and controls. Within the FS group, HHV-6B infection was associated with FSE, suggesting HHV-6B infections could play a role in the pathogenesis of FSE.

Global Health: Pediatric Neurology.

Neurologic disorders contribute significantly to both morbidity and mortality among children in resource-limited settings, but there are a few succinct studies summarizing the epidemiology of neurologic disorders in these settings. A review of available literature was performed to identify data on the prevalence, etiology, outcomes, and treatment of neurologic disorders in children in resource-limited settings. The burden of neurologic disorders in children is high in resource-limited settings. Barriers to optimal care include lack of trained personnel, limited access to diagnostic technology, and limited availability of drugs used to treat common conditions. Several solutions have been suggested to deal with these challenges including increased collaborations to train neurologists willing to practice in resource-limited settings and increased training of physician extenders or community health workers. Further studies are necessary to improve our understanding of the epidemiology of neurologic disorders in resource-limited settings. Future epidemiologic studies should incorporate multiple countries in resource-limited settings and utilize standardized definitions and methodologies to enable comparison across regions.

Management of acute seizures in children: A review with special consideration of care in resource-limited settings.

INTRODUCTION: We sought to review recent evidence-based guidelines and where applicable, primary data to extrapolate insights into the appropriate management of acute seizures in children in resource-limited settings. METHODS: PubMed and Google scholar searches were conducted with attention to publications from the last three to five years, including a focused search for acute seizure management guidelines relevant to resource limited settings. Since all guidelines to date, except the World Health Organization's, assume ready access to invasive ventilation and advanced diagnostic testing, guidelines and primary data were used to propose management appropriate for resource-limited settings where respiratory suppression from treatment presents a major challenge in management. RESULTS: Acute seizures are among the commonest medical emergencies encountered in the African settings. Seizure management must occur simultaneously with the diagnostic assessment, which should include addressing life threatening causes (e.g. hypoglycaemia, malaria) and with attention given to the most likely aetiology in a particular region or setting. For ongoing seizures, initial treatment with benzodiazepines is indicated. There is evidence of efficacy for several agents and delivery modes. Longer-acting antiepileptic drugs (AEDs) should be on hand if acute seizures fail to respond to two doses of benzodiazepines. There is little direct evidence comparing the relative efficacy of different long-acting AEDs for acute seizure management in African children. Findings suggest that generalising data from Western settings, where different aetiologies and risk factors for seizures prevail, may be inappropriate. DISCUSSION: Though treatment options and diagnostics may be dictated by available medications and capacity, it is possible for virtually any healthcare setting to develop a relevant and feasible local guideline for seizure management. Clear specifications on when to refer to a higher level of care should be part of the care plan.

Management of acute seizures in children: a review with special consideration of care in resource-limited settings

Introduction:We sought to review recent evidence-based guidelines and where applicable, primary data to ex-trapolate insights into the appropriate management of acute seizures in children in resource-limited settings.Methods:PubMed and Google scholar searches were conducted with attention to publications from the last three to five years, including a focused search for acute seizure management guidelines relevant to resource limited settings. Since all guidelines to date, except the World Health Organization's, assume ready access to invasive ventilation and advanced diagnostic testing, guidelines and primary data were used to propose managementappropriate for resource-limited settings where respiratory suppression from treatment presents a major challenge in management.Results:Acute seizures are among the commonest medical emergencies encountered in the African settings.Seizure management must occur simultaneously with the diagnostic assessment, which should include addres-sing life threatening causes (e.g. hypoglycaemia, malaria) and with attention given to the most likely aetiology ina particular region or setting. For ongoing seizures, initial treatment with benzodiazepines is indicated. There is evidence of efficacy for several agents and delivery modes. Longer-acting antiepileptic drugs (AEDs) should beon hand if acute seizures fail to respond to two doses of benzodiazepines. There is little direct evidence comparing the relative efficacy of different long-acting AEDs for acute seizure management in African children.Findings suggest that generalising data from Western settings, where different aetiologies and risk factors for seizures prevail, may be inappropriate.Discussion: Though treatment options and diagnostics may be dictated by available medications andcapacity, it is possible for virtually any healthcare setting to develop a relevant and feasible local guideline for seizure management. Clear specifications on when to refer to a higher level of care should be part of the care plan

A pediatric epilepsy diagnostic tool for use in resource-limited settings: A pilot study.

OBJECTIVE: It is estimated that nearly 80% of the 50 million people affected with epilepsy globally live in regions where specialist care and diagnostic tests are scarce and care is often delivered through a primary health provider with limited training. To improve diagnostic accuracy of the history and physical examination, we developed and piloted a questionnaire to discriminate between focal versus generalized epilepsy, with the future goal to guide medication choices. METHODS: Through literature review and retrospective chart review of 75 children with epilepsy at Boston Children's Hospital, a 15-item questionnaire was developed. Simple motor seizures were excluded for the purposes of this questionnaire. The questionnaire was then translated in local dialects and prospectively validated at Muhimbili National Hospital in Dar Es Salaam, Tanzania, and University Teaching Hospital in Lusaka, Zambia. Children 6months-18years of age with suspected or active epilepsy were identified, and a nonphysician administered the questionnaire to the patient's caregiver. Next, each patient was evaluated by a pediatric neurologist blinded to the questionnaire results, and together with locally obtained but remotely interpreted EEG, an electroclinical diagnosis was made. The questionnaire data were compared with this clinical gold standard. RESULTS: A total of 59 children participated: 28 from Tanzania and 31 from Zambia. Sixteen patients were excluded: 5 were excluded because of incomplete data, and 11 did not meet criteria for epilepsy based on initial screening questions. Of the remaining 43 patients, 28 had focal or multifocal epilepsy (65%), and 15 (35%) had generalized epilepsy. The questionnaire had a sensitivity of 78% and positive predictive value of 81.5%. Data were analyzed using a Rasch model, testing the questionnaire's internal consistency, reliability, and its discriminative validity in classifying focal versus generalized epilepsy against an electroclinical diagnosis. The mean epilepsy score for focal epilepsy was 0.084 logits compared with -1.147 logits for generalized epilepsy, demonstrating a large effect size [F (1, 41)=13.490, p<0.001]. CONCLUSIONS: Our questionnaire provides a straightforward method to improve diagnostic accuracy, and could assist in bridging the diagnostic gap in pediatric epilepsy in resource-limited settings. This tool was specifically designed to be easily implemented by any healthcare provider. This pilot study prompts broader prospective validation in additional settings for further refinement, and for performance assessment of impact on provider's practice, ability to guide medication choices, and ultimately improve treatment outcomes in resource-limited regions.

Supraventricular Tachycardia During Status Epilepticus in Dravet Syndrome: A Link Between Brain and Heart?

BACKGROUND: The possibility that epileptic seizures and arrhythmias are different clinical manifestations of a common channelopathy is an interesting but unproved hypothesis. Patients with Dravet syndrome show heart rate variability and affected individuals with arrhythmias have also been documented. The possibility that a genetic mutation affecting sodium channel functions may predispose to both Dravet syndrome and arrhythmogenic disorders is an interesting hypothesis. PATIENT PRESENTATION: We describe a 5-month-old girl with Dravet syndrome who presented with paroxysmal supraventricular tachycardia during status epilepticus. She presented to the hospital the first time with afebrile tonic-clonic seizures and then several subsequent times with status epilepticus confirmed with electroencephalography. During two of these episodes she also exhibited paroxysmal supraventricular tachycardia. She received propofol for status epilepticus and adenosine for the arrhythmia. A clinical and genetic (denovo mutation of a sodium channel, SCN1A) diagnosis of Dravet syndrome was made. CONCLUSIONS: Our patient supports the hypothesis that SCN1A mutation might have a role as a common substrate to both epilepsy and cardiac arrhythmia. More studies are needed to better assess genetic, cardiac, respiratory, and autonomic dysfunction in patients with Dravet syndrome.