Gretchen L. Birbeck

Seizure Reduction and Quality of Life Improvements in People with Epilepsy

Summary:  Purpose: Previous research suggests that seizure freedom may be necessary to improve health‐related quality of life (HRQOL) for epilepsy surgery patients, but little is known regarding the seizure‐frequency reduction needed to improve HRQOL among medically treated individuals.

Evidence-based guidelines for mental, neurological, and substance use disorders in low- and middle-income countries: summary of WHO recommendations.

Shekhar Saxena and colleagues summarize the recent WHO Mental Health Gap Action Programme (mhGAP) intervention guide that provides evidence-based management recommendations for mental, neurological, and substance use (MNS) disorders.

Epilepsy-associated stigma in sub-Saharan Africa: the social landscape of a disease.

Many studies in developed regions of the world have confirmed that stigma contributes substantially to the psychological and social burden of epilepsy. Relatively few studies of epilepsy-associated stigma have been conducted in Africa, where much of the worlds burden of epilepsy exists. In sub-Saharan Africa (SSA), particularly in rural regions, close family ties, communal living situations, and traditional belief systems undoubtedly influence the expression of stigmatization. A review of the epidemiologic, anthropologic, and sociologic studies of epilepsy in SSA provides significant insights into how people with epilepsy (PWE) are perceived by their communities and families and how these perceptions translate into limited social and economic opportunities and possibly worsen the physical vulnerability of PWE in this region. The medical community is not exempt from the social process of stigmatization, and poor public health infrastructure and medical services undoubtedly contribute to the cycle of epilepsy-associated stigma through wide treatment gaps, poor seizure control, and high rates of seizure-related injury. In this review, we extrapolate data from existing studies of epilepsy in SSA coupled with our own experience providing epilepsy care in the region to give an overview of the social landscape of this common, devastating condition.

A Systematic Review of Neuroimaging for Cerebral Palsy

The American Academy of Neurology now recommends that all cases of cerebral palsy of unknown origin undergo neuroimaging. Controversy surrounds this recommendation because of concerns about the adequacy of the supporting evidence. This article reviews the evidence provided by magnetic resonance imaging (MRI) and computed tomography (CT) imaging studies in cerebral palsy and discusses the potential benefits of imaging, techniques in current use, and future directions, with a focus on improving etiologic understanding. Most (83%) children with cerebral palsy have abnormal neuroradiological findings, with white matter damage the most common abnormality. Combined gray and white matter abnormalities are more common among children with hemiplegia; isolated white matter abnormalities are more common with bilateral spasticity or athetosis, and with ataxia; isolated gray matter damage is the least common finding. About 10% of cerebral palsy is attributable to brain malformations, and 17% of cerebral palsy cases have no abnormality detectable by conventional MR or CT imaging. Although neuroimaging studies have increased our understanding of the abnormalities in brain development in cerebral palsy, they are less informative than they might be because of 4 common problems: (1) inappropriate assignment of etiology to morphologic findings, (2) inconsistent descriptions of radiologic findings, (3) uncertain relationship of pathologic findings to brain insult timing estimates, and (4) study designs that are not based on generalizable samples. Neuroimaging is not necessarily required for diagnosis of cerebral palsy because the disorder is based on clinical findings. The principal contribution of imaging is to the understanding of etiology and pathogenesis, including ruling in or out conditions that may have implications for genetic counseling, such as malformations. In the future, as more sophisticated imaging procedures are applied to cerebral palsy, specific morphologic findings may be linked to etiologic events or exposures, thus leading to potential pathways for prevention.

Blantyre Malaria Project Epilepsy Study (BMPES) of neurological outcomes in retinopathy-positive paediatric cerebral malaria survivors: a prospective cohort study

Summary Background Cerebral malaria, a disorder characterised by coma, parasitaemia, and no other evident cause of coma, is challenging to diagnose definitively in endemic regions that have high rates of asymptomatic parasitaemia and limited neurodiagnostic facilities. A recently described malaria retinopathy improves diagnostic specificity. We aimed to establish whether retinopathy-positive cerebral malaria is a risk factor for epilepsy or other neurodisabilities. Methods Between 2005 and 2007, we did a prospective cohort study of survivors of cerebral malaria with malaria retinopathy in Blantyre, Malawi. Children with cerebral malaria were identified at the time of their index admission and age-matched to concurrently admitted children without coma or nervous system infection. Initially matching of cases to controls was 1:1 but, in 2006, enrolment criteria for cerebral malaria survivors were revised to limit inclusion to children with cerebral malaria and retinopathy on the basis of indirect ophthalmoscopic examination; matching was then changed to 1:2 and the revised inclusion criteria were applied retrospectively for children enrolled previously. Clinical assessments at discharge and standardised nurse-led follow-up every 3 months thereafter were done to identify children with new seizure disorders or other neurodisabilities. A Kaplan-Meier survival analysis was done for incident epilepsy. Findings 132 children with retinopathy-positive cerebral malaria and 264 age-matched, non-comatose controls were followed up for a median of 495 days (IQR 195–819). 12 of 132 cerebral malaria survivors developed epilepsy versus none of 264 controls (odds ratio [OR] undefined; p<0·0001). 28 of 121 cerebral malaria survivors developed new neurodisabilities, characterised by gross motor, sensory, or language deficits, compared with two of 253 controls (OR 37·8, 95% CI 8·8–161·8; p<0·0001). The risk factors for epilepsy in children with cerebral malaria were a higher maximum temperature (39·4°C [SD 1·2] vs 38·5°C [1·1]; p=0·01) and acute seizures (11/12 vs 76/120; OR 6·37, 95% CI 1·02–141·2), and male sex was a risk factor for new neurodisabilities (20/28 vs 38/93; OR 3·62, 1·44–9·06). Interpretation Almost a third of retinopathy-positive cerebral malaria survivors developed epilepsy or other neurobehavioural sequelae. Neuroprotective clinical trials aimed at managing hyperpyrexia and optimising seizure control are warranted. Funding US National Institutes of Health and Wellcome Trust.

Migraine: the seventh disabler

With the agreement of the Editors-in-Chief, this editorial is published simultaneously by Cephalalgia, Headache and The Journal of Headache and Pain. On 15th December 2012, a special edition of Lancet published the principal findings of the Global Burden of Disease Survey 2010 (GBD2010). Few reports are likely to have more profound meaning for people with headache, or carry greater promise for a better future, than the seven papers (and one in particular [1]) that were presented. GBD2010 was not the first such survey to be conducted, nor the first to give some recognition to the burden of migraine. The Global Burden of Disease Survey 2000 (GBD2000), conducted 12 years ago by the World Health Organization (WHO), listed migraine as the 19th cause of disability in the world, responsible for 1.4% of all years of life lost to disability (YLDs) [2]. This finding has been cited repeatedly ever since; it has fuelled attempts to generate political acceptance of headache as a public-health priority [3], and given credibility to calls for greater investment in headache care and research. It pushed headache into WHO’s field of view, and became an essential part of the platform on which the Global Campaign against Headache has since been built [3-5]. In spite of all this, GBD2000 considerably underreported the disability that migraine imposed on people throughout the world, and gave a very poor account of headache disorders collectively. The evidence was not there. For more than half the world’s population, estimates for migraine were based on very little: data of acceptable quality were not in existence for China, India and most other countries in South East Asia, most of Africa, all of the Eastern Mediterranean and all of eastern Europe [6]. Headache disorders other than migraine did not feature in GBD2000 at all; for these disorders, at that time, dependable evidence was lacking everywhere. Filling this evidence gap has been a priority of the Global Campaign in its first years [7]. As a result, GBD2010 has been much better informed and built on much sounder foundations than its predecessor (we return to this point later). GBD2010 was not a simple update of GBD2000, but a complete rerun: an entirely new world survey. Working with many partners, the Global Campaign against Headache being one, it took from the world literature all the epidemiological evidence pertaining to burdensome diseases, assessed it for quality and derived from it, for each of 21 world regions, best age-related estimates of prevalence. Like GBD2000, it measured burden in disability-adjusted life years (DALYs), separated into the two components of YLDs and years of life lost to early mortality (YLLs); for headache, only the former are relevant. New disability weights (DWs) were assigned to each disease: lay descriptions of the various health states that were predictable sequelae of each disease were fed into a web-based worldwide consultation, which conducted an iterative series of comparisons, one health state with another. For migraine and tension-type headache (TTH), descriptions were agreed of average cases and three health states of each: ictal (during attacks), interictal (between attacks), and the health state associated with medication-overuse headache (MOH), which was considered as a potential complication of either. Information from published studies on frequency and duration of migraine or TTH episodes was pooled in order to estimate the average proportions of time (pT) spent in the ictal as opposed to interictal state. MOH was assumed to be continuous (pT=1) when present. YLDs for each of these states were then derived as products of prevalence, pT and DW, and for each disease as the sum of YLDs for each health state. Data were included from 84 studies of migraine in 43 countries in 16 of the 21 world regions, and from 45 studies of TTH in 34 countries in 13 world regions. TTH (estimated global prevalence 20.1%) and migraine (14.7%) ranked respectively as second and third most common diseases in the world (behind dental caries) in both males and females. For migraine, the estimated proportion of time spent in the ictal state was 5.3%, and the DW assigned to migraine episodes was 0.433 (43.3% disability). On the basis of ictal disability alone, migraine was ranked seventh highest among specific causes of disability globally (responsible for 2.9% of all YLDs), and in the top ten causes of disability in 14 of the 21 world regions, showing little evidence of a gradient falling from west to east or of being a disorder preferentially of rich countries. Migraine was, by a wide margin, the leading cause of disability among neurological disorders, accounting for over half of all YLDs attributed to these. For TTH, the estimated proportion of time spent with headache was 2.4%, and the DW assigned to headache episodes was 0.040 (4% disability). TTH accounted for only 0.23% of all YLDs, much less than predicted [6], which undoubtedly was because of the very low DW accorded to the ictal state. Regrettably, GBD2010 is still an incomplete account of the global burden of headache, and it continues to underestimate the disability arising from headache disorders. TTH got in, but MOH, which would probably have added much more substantially to the total YLDs, was excluded late in the survey for reasons not made clear and despite the evidence submitted in support of it. Also at a late-stage, the inclusion of interictal disability was considered inconsistent with measurements made of other chronic episodic conditions, which penalized migraine more than TTH. Even so, this very high-profile survey of the world’s causes of ill health better recognizes headache than anything before, and this is a big step forward. We might be satisfied by this; but rather we should be appalled. GBD measures disease burden as it is – alleviated by whatever treatments are made available. Headache disorders are among the top ten causes of disability because they are common and disabling; that is clear. Headache is one of the most frequent medical complaints: almost everybody has experienced it, at least 10% of adults everywhere are sometimes disabled by it, and up to 3% live with it on more days than not [6]. But for what conceivable reason do headache disorders remain among these ignominious top ten when they are largely treatable? Another recent global survey, conducted collaboratively by WHO and Lifting The Burden, described “worldwide neglect of major causes of public ill-health, and the inadequacies of responses to them in countries throughout the world” [8]. It drew attention to the very large numbers of people disabled by headache who do not receive effective health care. The barriers responsible for this might vary throughout the world, but poor awareness of headache in a context of limited resources generally – and in health care in particular – was constantly among them [8]. The consequences are inevitable: illness that can be relieved is not, and heavy burdens, both individual and societal [9], persist when they can be mitigated. The findings of GBD2010 sadly reflect this. GBD2010 sends out a clarion call, conveying a message of which governments need to take note [3]. Experience suggests this call will need constantly to be re-echoed, but the opportunity to use GBD2010 – for a better future for people with headache – must not be missed.

The social and economic impact of epilepsy in Zambia: a cross-sectional study

BACKGROUND Among the 40 million people with epilepsy worldwide, 80% reside in low-income regions where human and technological resources for care are extremely limited. Qualitative and experiential reports indicate that people with epilepsy in Africa are also disadvantaged socially and economically, but few quantitative systematic data are available. We sought to assess the social and economic effect of living with epilepsy in sub-Saharan Africa. METHODS We did a cross-sectional study of people with epilepsy concurrently matched for age, sex, and site of care to individuals with a non-stigmatised chronic medical condition. Verbally administered questionnaires provided comparison data for demographic characteristics, education, employment status, housing and environment quality, food security, healthcare use, personal safety, and perceived stigma. FINDINGS People with epilepsy had higher mean perceived stigma scores (1.8 vs 0.4; p<0.0001), poorer employment status (p=0.0001), and less education (7.1 vs 9.4 years; p<0.0001) than did the comparison group. People with epilepsy also had less education than their nearest-age same sex sibling (7.1 vs 9.1 years; p<0.0001), whereas the comparison group did not (9.4 vs 9.6 years; p=0.42). Housing and environmental quality were poorer for people with epilepsy, who had little access to water, were unlikely to have electricity in their home (19%vs 51%; p<0.0001), and who had greater food insecurity than did the control group. During pregnancy, women with epilepsy were more likely to deliver at home rather than in a hospital or clinic (40%vs 15%; p=0.0007). Personal safety for people with epilepsy was also more problematic; rape rates were 20% among women with epilepsy vs 3% in the control group (p=0.004). INTERPRETATION People with epilepsy in Zambia have substantially poorer social and economic status than do their peers with non-stigmatised chronic medical conditions. Suboptimum housing quality differentially exposes these individuals to the risk of burns and drowning during a seizure. Vulnerability to physical violence is extreme, especially for women with epilepsy.

Brain Swelling and Death in Children with Cerebral Malaria

BACKGROUND Case fatality rates among African children with cerebral malaria remain in the range of 15 to 25%. The key pathogenetic processes and causes of death are unknown, but a combination of clinical observations and pathological findings suggests that increased brain volume leading to raised intracranial pressure may play a role. Magnetic resonance imaging (MRI) became available in Malawi in 2009, and we used it to investigate the role of brain swelling in the pathogenesis of fatal cerebral malaria in African children. METHODS We enrolled children who met a stringent definition of cerebral malaria (one that included the presence of retinopathy), characterized them in detail clinically, and obtained MRI scans on admission and daily thereafter while coma persisted. RESULTS Of 348 children admitted with cerebral malaria (as defined by the World Health Organization), 168 met the inclusion criteria, underwent all investigations, and were included in the analysis. A total of 25 children (15%) died, 21 of whom (84%) had evidence of severe brain swelling on MRI at admission. In contrast, evidence of severe brain swelling was seen on MRI in 39 of 143 survivors (27%). Serial MRI scans showed evidence of decreasing brain volume in the survivors who had had brain swelling initially. CONCLUSIONS Increased brain volume was seen in children who died from cerebral malaria but was uncommon in those who did not die from the disease, a finding that suggests that raised intracranial pressure may contribute to a fatal outcome. The natural history indicates that increased intracranial pressure is transient in survivors. (Funded by the National Institutes of Health and Wellcome Trust U.K.).

Epilepsy Care in Zambia: A Study of Traditional Healers

Summary:  Purpose: Most people with epilepsy (PWE) reside in developing countries with limited access to medical care. In sub‐Saharan Africa (SSA), traditional healers (THs) play a prominent role in caring for PWE, yet little is known about epilepsy care by THs. We conducted a multimethod, qualitative study to better understand the epilepsy care delivered by THs in Zambia.

Epilepsy prevalence in rural Zambia: a door-to-door survey

Objectives  To identify people with epilepsy (PWE) in our Zambian catchment area of 55 000 people.