Diagnosis and Classification of Pediatric Epilepsy in Sub-Saharan Africa: A Comprehensive Review

Abstract

Background/Objectives: Epilepsy is a major public health issue in Sub-Saharan Africa, particularly among children, due to limited healthcare resources, socioeconomic inequalities, and cultural stigma that often result in underdiagnosis and undertreatment. This review examines pediatric epilepsy’s diagnosis, classification, and management in this setting, highlighting the need for culturally appropriate interventions to improve care quality and address these challenges. Methods: A review of the literature was conducted using MEDLINE, Embase, Scopus, and Web of Science databases to identify pertinent studies published between 2013 and 2024. This review included studies examining the epidemiology, seizure classification and etiologies of epilepsy among children in Sub-Saharan Africa. Results: This review revealed higher incidence and prevalence of epilepsy in Sub-Saharan Africa compared to high-income countries, primarily attributable to factors such as infectious diseases, perinatal injuries, and limited diagnostic resources. The most frequently reported types of epilepsy were generalized and focal seizures, with significant etiological contributions from structural and infectious causes, including nodding syndrome and HIV-related epilepsy. The treatment gap remains considerable, with up to 80% of children not receiving appropriate antiseizure medications. Conclusions: The diagnosis and treatment of epilepsy in pediatric populations in Sub-Saharan Africa is complicated by several factors, including cultural stigma and the lack of adequate healthcare infrastructure. There is an urgent need for culturally tailored diagnostic tools, improved access to affordable treatments, and public health initiatives aimed at reducing stigma. Addressing these gaps through enhanced research, improved healthcare access, and targeted educational campaigns is crucial for improving the quality of life for children with epilepsy.

Full text

Citation: Di Noia, S.; Bonezzi, L.;
Accorinti, I.; Bartolini, E. Diagnosis
and Classification of Pediatric
Epilepsy in Sub-Saharan Africa: A
Comprehensive Review. J. Clin. Med.
2024,13, 6396. https://doi.org/
10.3390/jcm13216396
Academic Editor: Zhen Hong
Received: 23 September 2024
Revised: 9 October 2024
Accepted: 12 October 2024
Published: 25 October 2024
Copyright: © 2024 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
Journal of
Clinical Medicine
Review
Diagnosis and Classification of Pediatric Epilepsy in
Sub-Saharan Africa: A Comprehensive Review
Sofia Di Noia 1,2, Linda Bonezzi 3,4,5 , Ilaria Accorinti 4,5 and Emanuele Bartolini 2, 4, *
1Neuropediatric Unit, Woman and Child Department, Polyclinic of Foggia, 71122 Foggia, Italy;
sofiadinoianpi@gmail.com
2Tuscany PhD Programme in Neurosciences, 50139 Florence, Italy
3School of Medicine, Faculty of Medicine and Biomedical Sciences, The University of Queensland,
Brisbane 4072, Australia; linda.bonezzi@fsm.unipi.it
4Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, 56128 Pisa, Italy;
ilaria.accorinti@fsm.unipi.it
5Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
*Correspondence: emanuele.bartolini@fsm.unipi.it
Abstract: Background/Objectives: Epilepsy is a major public health issue in Sub-Saharan Africa,
particularly among children, due to limited healthcare resources, socioeconomic inequalities, and
cultural stigma that often result in underdiagnosis and undertreatment. This review examines
pediatric epilepsy’s diagnosis, classification, and management in this setting, highlighting the need for
culturally appropriate interventions to improve care quality and address these challenges. Methods:
A review of the literature was conducted using MEDLINE, Embase, Scopus, and Web of Science
databases to identify pertinent studies published between 2013 and 2024. This review included studies
examining the epidemiology, seizure classification and etiologies of epilepsy among children in Sub-
Saharan Africa. Results: This review revealed higher incidence and prevalence of epilepsy in Sub-
Saharan Africa compared to high-income countries, primarily attributable to factors such as infectious
diseases, perinatal injuries, and limited diagnostic resources. The most frequently reported types of
epilepsy were generalized and focal seizures, with significant etiological contributions from structural
and infectious causes, including nodding syndrome and HIV-related epilepsy. The treatment gap
remains considerable, with up to 80% of children not receiving appropriate antiseizure medications.
Conclusions: The diagnosis and treatment of epilepsy in pediatric populations in Sub-Saharan Africa
is complicated by several factors, including cultural stigma and the lack of adequate healthcare
infrastructure. There is an urgent need for culturally tailored diagnostic tools, improved access to
affordable treatments, and public health initiatives aimed at reducing stigma. Addressing these
gaps through enhanced research, improved healthcare access, and targeted educational campaigns is
crucial for improving the quality of life for children with epilepsy.
Keywords: childhood epilepsy; LMIC; pediatric; epidemiology; challenges
1. Introduction
Epilepsy is a neurological disorder characterized by the recurrence of unprovoked
seizures and by the associated neurobiological, cognitive, psychological, and social conse-
quences [1]. It constitutes a major public health challenge worldwide.
The World Health Organization (WHO) estimates that about 5 million people are
diagnosed with epilepsy each year. Global lifetime prevalence is higher than 50 million,
making epilepsy the second most common neurological disorder after stroke. Nearly 80% of
people with epilepsy (PWE) live in low- and middle-income countries (LAMICs), where the
epidemiological and social burden of epilepsy is significantly higher [
2
,
3
]. The underlying
etiology is variable—spanning from genetic, brain structural, infectious, metabolic, immune,
or unknown causes—and depends on the geographical location. In high-income countries
J. Clin. Med. 2024,13, 6396. https://doi.org/10.3390/jcm13216396 https://www.mdpi.com/journal/jcm

J. Clin. Med. 2024,13, 6396 2 of 32
(HICs), acquired brain lesions (e.g., stroke, brain tumors) play a major role, whilst in
LAMICs, infectious disorders and traumatic brain injuries are prevailing [4].
To diagnose epilepsy and to ascertain the etiology can be difficult tasks, especially in
LAMICs, where socioeconomic and cultural constraints can be obstacles to the recognition
and acceptance of the disease.
PWE must face a wide array of hurdles for wellbeing, both related to the largely
unpredictable nature of seizures themselves and also to the adverse events of medications,
social limitations, public stigma, psychiatric, cognitive, and somatic comorbidities. These
factors often hamper a satisfiable quality of life and can be especially dooming for children.
At the pediatric age, coping strategies to prevent social isolation and discrimination are
frailer. Mental health and psychological wellbeing can be neglected in geographical regions
affected by economic difficulties or faraway from metropolitan centers such as many
African regions, especially in rural areas.
Indeed, epilepsy can have a devastating impact on individuals and families, leading
to health, social, psychological, and economic hardship. Furthermore, epilepsy affects
not only the wellbeing of the individual but also influences resource allocation for health
systems that have to manage a wide number of critical conditions.
Epilepsy carries a significant impact on disability-adjusted life years (DALYs)—a
measure of years lost due to ill health, disability, or early death [
5
]. In 2016, epilepsy was
associated with more than 13 million DALYs. While this figure appears in a steady reduc-
tion trend for HICs, LAMICs still struggle with an unchanged health and socioeconomic
impact [5–8].
Such complex background mandates us to enhance the understanding of the specific
challenges for PWE in Africa.
Although the International League Against Epilepsy (ILAE) Pediatric Commission
Research Advocacy Task Force has recently recognized a remarkable increase in epilepsy
research capability in Africa over the past 30 years, there remains a significant need to
strengthen the region’s capacity, both in terms of study quality and broader coverage of
relevant areas [9].
In the current review, we focus on the available evidence on the epidemiology and
clinical characterization of epilepsy, the subjective experiences of patients and caregivers,
the challenges and barriers to care, the cultural factors that need to be considered when
developing interventions, and the best practices for providing epilepsy care in Africa. Our
purpose is to provide a state-of-the-art scenario to raise awareness on the topic, with special
attention to consider culturally appropriate interventions.
We aim particularly to describe the specific challenges in diagnosis and classification
that are fundamental to establish the correct treatment and management of children with
epilepsy in Sub-Saharan Africa.
2. Materials and Methods
The current review was conducted according to the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses statement using the extension checklist for scoping
reviews (PRISMA-ScR) [10].
To identify relevant papers, we systematically searched MEDLINE (accessed by
PubMed), Embase, Scopus and Publons/Web of Science databases for full-text articles
published from 2013 up to 8 August 2024, using the following search terms: epidemiol*
AND africa* AND child* AND epilep*.
Using automated filters, we excluded (i) abstract and conference papers and
(ii) studies published in language other than English. We then manually assessed the
titles and abstracts of the retrieved papers to exclude those unrelated to the topic of interest.
Endnote web reference manager was used to exclude duplicate papers. The full text of
all potentially eligible articles and their Supplementary Information were independently
assessed by two authors (S.D.N. and E.B.) and summarized through joint discussion. In

J. Clin. Med. 2024,13, 6396 3 of 32
the final analysis, we included 11 studies with focus on seizure classification, 14 studies on
epilepsy epidemiology, and 11 studies on epilepsy etiology.
3. Results
3.1. Epidemiology: Incidence and Prevalence
Most incidence studies have been conducted in HICs, often with a suboptimal design
such as a retrospective observation rather than community-based surveys. Nevertheless,
available data from Africa have steadily increased and are not to be neglected. Incidence
studies are important for identifying risk factors as well as for providing information on
prognosis, assessing the number of new cases of epilepsy in a well-defined population
during a specified period (e.g., 1 year or lifetime).
In a systematic review and meta-analysis study, Fiest et al. calculated the incidence
rate of epilepsy to be 61.4 per 100,000 person-years (95% CI 50.7–74.4), with higher values
in LAMICs compared to HICs (139 vs. 48.9 per 100,000 person-years) [
11
] (Table 1). Such
difference highlights the different composition of the population at risk as well as the
heterogeneity of causative factors [
11
]. In HICs, the incidence follows a typical U-shape,
with peaks in early childhood and in the elderly. Conversely, in LAMICs the epilepsy
incidence is definitely higher in early childhood and progressively decreases over time. In
Sub-Saharan Africa (SSA), the vast majority of people with incident epilepsy are younger
than 20 years old, and the elderly-age peak is absent [
12
]. This may be due to the lower life
expectancy, with consequent less exposure to the typical factors promoting elderly-onset
epilepsy in HICs (e.g., cerebrovascular and neurocognitive diseases), in addition to the
increased mortality rate associated with epilepsy and its underlying causes. Perinatal
causes such as birth asphyxia are a powerful driver of seizures in Africa that may also
affect mortality [
13
]. Of note, Fiest et al. found that cumulative incidence was not differ-
ent worldwide; the rare occurrence of elderly-onset epilepsy in LAMICs appears to be
counterbalanced by a higher peak in childhood [11].
Table 1. A comprehensive overview of the epidemiology of epilepsy. The table provides an overview
of the prevalence and incidence rates observed in different Sub-Saharan countries. Wherever feasible,
comparisons are drawn with global rates or rates from other industrialized countries that are not
tropical. Furthermore, specific etiologies are referenced in the text. LMIC = low- and middle-income
country; HIC = high-income country; ACE = active convulsive epilepsy.
Study Topic and Type of Study Main Findings
Fiest et al., 2017 [11]
International prevalence and incidence of
epilepsy, systematic review and
meta-analysis.
Worldwide pooled point prevalence of active epilepsy
6.38 per 1000 persons and pooled incidence rate of
epilepsy 61.44 per 100,000 person-years.
LMIC prevalence of active epilepsy 6.68 per 1000
persons compared to HIC prevalence of active epilepsy
5.49 per 1000 persons.
Preux et al., 2005 [12]Review of epidemiology and etiology of
epilepsy in Sub-Saharan Africa.
Annual incidences of 63–158 per 100,000 inhabitants,
higher than industrialized countries in nontropical areas
of 40–70 per 100,000 inhabitants.
Prevalence of epilepsy variable even in the same country
with a median prevalence found in door-to-door studies
of 15 per 1000 people.
Beghi et al., 2020 [4]Review of global epidemiology of
epilepsy.
Incidence higher in LMICs than HICs, 139.0 vs. 48.9. As
the incidence of epilepsy appears higher in most LMICs,
the overlapping prevalence can be explained by
misdiagnosis, acute symptomatic seizures and
premature mortality.
Kaiser et al., 1998 [14]Incidence of epilepsy in Uganda, related
to onchocerciasis.
Crude incidence rate of 215 per 100,000 person-years
with a significant difference between zones of high and
low onchocerciasis endemicity.

J. Clin. Med. 2024,13, 6396 4 of 32
Table 1. Cont.
Study Topic and Type of Study Main Findings
Rwiza et al., 1992 [15]
Prevalence and incidence of epilepsy in a
rural Tanzanian District.
Prevalence of active epilepsy 10.2 in 1000, ranging from
5.1 to 37.1 in 1000 (age-adjusted 5.8–37.0).
In a 10-year period (1979–1988), annual incidence of 73.3
in 100,000.
Tekle-Haimanot et al.,
1997 [16]
Incidence of Epilepsy in Rural Central
Ethiopia.
Annual incidence of 64 in 100,000 inhabitants. The
corresponding rate for males was 72 (CI 42–102); for
females, it was 57 (CI 31–84). The highest age-specific
incidence occurred in the youngest age groups (0–9
years).
Edwards et al., 2008 [17]Prevalence and risk factors for ACE in a
rural district of Kenya.
Overall prevalence of ACE 2.9 per 1000 people.
On a 5 year cut off for date of last seizure, unadjusted
prevalence of ACE 3.1 per 1000 (2.8–3.4 per 1000).
Garrez et al., 2024 [18]Epilepsy prevalence in rural Southern
Rwanda.
Crude, unadjusted prevalence of lifetime epilepsy 76.2
per 1000 people. Prevalence adjusted for screening
sensitivity 80.1 per 1000 people when. Crude prevalence
standardized to the age distribution from Rwanda 78.3
per 1000 when, 89.1 per 1000 from the United States, and
85.3 per 1000 worldwide.
Mwanga et al., 2024 [19]Prevalence epilepsy in urban informal
settlements in Kenya.
Crude prevalence of epilepsy 9.4 per 1000 people.
Prevalence adjusted for attrition 11.5 per 1000 people
and 11.9 per 1000 people (11.0–12.8) when adjusted for
attrition and sensitivity.
Biset et al., 2024 [20]
Systematic review and meta-analysis of
prevalence, incidence, and trends of
epilepsy among children and adolescents
in Africa.
Pooled prevalence of cumulative epilepsy was 17.3 per
1000 children. Pooled prevalence of lifetime and ACE
were 18.6 and 6.8 per 1000 children respectively. Pooled
prevalence of unclassified epilepsy was 45.5 per 1000
children. Pooled prevalence of epilepsy in high parasite
endemic areas was 44 per 1000 children. Pooled
prevalence of epilepsy in the general population was 8
per 1000 children. The highest prevalence of epilepsy
was reported in Southern African countries (129.3/1000)
followed by Central African countries (32.3/1000) and
Northern African countries (24.1/1000).
However, the epidemiological view of epilepsy according to socioeconomic and geo-
graphical location can be blurred by sampling biases. The incidence might be overestimated
in world regions characterized by limited diagnostic resources and less stringent epidemi-
ological criteria [
4
]. With this regard, studies conducted in resource-poor countries are
heterogeneous and partially conflicting. The incidence reported in Uganda [
14
] is twice that
of Tanzania [
15
] and of Ethiopia [
16
], which have figures comparable to those of Western
countries. Local etiological factors can also be involved, and the timing of the assessment
should be considered. In particular, infectious epidemic waves can drive peaks of incidence.
In Uganda, Kaiser et al. reported a much higher age-adjusted incidence in an onchocerciasis
endemic area than in nonendemic areas (232 vs. 77 per 100,000 person-years) [14].
Compared to studies on incidence, those on prevalence are more largely available.
These mostly employ cross-sectional designs (e.g., door-to-door surveys with standard-
ized validated screening questionnaires) that are easier and less expensive compared to
cohort studies.
Fiest et al. estimated an overall lifetime prevalence of epilepsy of 7.60 per 1000 popula-
tion (95% CI 6.17–9.38), higher in LAMICs (8.75 per 1000) compared to HICs (5.18 per 1000).
Smaller differences have been observed for point prevalence (6.68 vs. 5.49 per 1000) [
11
].
Studies from LAMICs tend to show a high prevalence in adolescents and young adults,
with much lower figures in the elderly [
17
], resembling the incidence pattern. As mentioned

J. Clin. Med. 2024,13, 6396 5 of 32
above, the demographic structure of the study population, the prevalence of environmental
risk factors, and the frailty of the local health system can be implicated. However, like
studies on incidence, prevalence studies in Africa can exhibit significant heterogeneity
between countries and even within the same country. Garrez et al. recently reported a very
high epilepsy prevalence by a door-to-door survey performed in southern rural Rwanda.
They reported a significant lifetime prevalence (76.2 per
1000 individuals
) and emphasized
the importance of carefully screening for nonconvulsive seizures, which may go unnoticed.
Notably, approximately one-fifth of the cases exhibited only nonconvulsive seizures [
18
].
The diagnostic difficulties for nonconvulsive epilepsy have also been reported in a recent
study performed in Kenya [19].
In the systematic review by Preux and Druet-Cabanac, the median prevalence was 15
per 1000 (range 5.2–70.0) in Sub-Saharan Africa [
12
]. Many of the included studies were
small and differed in methodology; focusing on the wider five studies (>15,000 subjects),
and prevalence ranged from 5.3 to 12.5 per 1000 [
12
]. The definition of epilepsy was not
systematically provided and only some studies focused on active epilepsy with precise
criteria (i.e., regular treatment with antiseizure medications or when the most recent seizure
has occurred within the last 5 years) [21].
Recently, Biset et al. performed a meta-analysis on the epidemiology of epilepsy
in Africa, focusing on children and adolescents. They found a pooled prevalence of
cumulative epilepsy of 17.3 per 1000 children (pooled prevalence of active epilepsy = 6.8;
lifetime epilepsy = 18.6 per 1000 children) and a pooled incidence of 2.5 per 1000 children.
The highest prevalence of epilepsy was reported in Southern African countries, with a rate
of 129.3 per 1000 children, followed by Central African countries, with a rate of 32.3 per
1000 children, and Northern African countries, at 24.1 per 1000 children [20].
3.2. Natural History, Prognosis, and Mortality of Epilepsy
The natural history of epilepsy can be partially understood through epidemiological
studies conducted in resource-poor settings. Epilepsy is generally considered a treatable
condition, with up to 80% of people achieving prolonged periods of seizure remission. In
some cases, individuals may even discontinue treatment and remain seizure-free. Based
on epidemiological evidence, Sander proposed four distinct courses for PWE: (i) Excellent
prognosis (20–30%): High likelihood of spontaneous remission, potentially not requiring
treatment. (ii) Good prognosis (30–40%): Seizures are typically well controlled with med-
ication, and treatment may be discontinued after a period of remission. (iii) Uncertain
prognosis (10–20%): Seizures may respond to medication, but there is a higher chance of
relapse after treatment withdrawal. (iv) Poor prognosis (20%): Seizures are less likely to
respond to medication, with a higher risk of recurrence [22].
The disease course varies according to the underlying cause, seizure type, and other
less predictable factors. The prognosis of untreated epilepsy can be reliably assessed only
in resource-poor settings where epilepsy is often untreated [
23
]. The prognosis can be
inferred by the comparison of the prevalence of active epilepsy to the incidence of epilepsy
in untreated PWE. In Ecuador, Placencia et al. estimated a remission rate of at least 50% [
24
].
Similar findings have been obtained in Africa, in a rural area of Malawi [
25
]. In spite of the
limited access to treatment, remission rates of epilepsy are comparable to those observed in
HICs [
4
]. However, these data need further confirmation due to the circumstantial nature
of the evidence, the use of nonstandard case definitions, and the lack of homogeneous
investigational procedures. In Africa, the proportion of people with active epilepsy not
currently receiving any antiseizure medication (ASM) treatment, or not currently receiving
adequate ASM treatment (i.e., “treatment gap”) is very high, with a median value of
80%, and up to 100% in Togo and Uganda [
26
]. PWE suffer a higher mortality rate than
those without epilepsy. Causes of death in PWE can be divided into epilepsy-related (e.g.,
sudden unexpected death in epilepsy, status epilepticus, drowning) and non-epilepsy-
related deaths (e.g., cerebrovascular disorders). Avoidable deaths in PWE are often caused
by the epilepsy itself, as the increased risk of death over the general population can be

J. Clin. Med. 2024,13, 6396 6 of 32
eliminated by achieving seizure freedom through effective treatment strategies. Non-
epilepsy-related deaths are, conversely, due to underlying disorders or to comorbidities
and cannot be directly modified by addressing the epilepsy course. According to Mbivzo
et al., the standardized mortality ratio (SMR) worldwide is higher for epilepsy-related
causes (median 3.8) than for unrelated causes (median 1.7), suggesting that more PWE
are likely to die prematurely from the first category [
27
]. In LAMICs, about half of cases
are due to epilepsy-related causes, especially status epilepticus and possible or probable
sudden unexpected death in epilepsy, followed by accidents [28].
People living in Africa experience the highest SMR (range 2.6–7.2, median 5.4). SMRs
are remarkable in children and young adults possibly due to both the comparatively lower
mortality rates in the general African populations of young age and to the remarkable risk
of death associated with symptomatic or structural/metabolic etiologies. In fact, these eti-
ologies (e.g., traumatic brain injury, possibly arising from vehicular collisions, occupational
accidents, sports, violence) are more common in males, who exhibit a higher risk than
women. Males may also be more exposed to hazardous occupations, yielding increased risk
of drowning, falls, or other fatal injuries consequent to seizures [
28
]. Drowning appears
to be a leading cause of death for PWE in Africa [
27
]. Mortality due to indirect causes
(accidents, drowning, burns) are relatively more common in Africa than in HIC and should
be prevented through education and safety measures [28].
3.3. Seizure Classification
From 2013 to 2023, there were only ten papers that reported data on seizure clas-
sification among children with epilepsy (CWE) in SSA (Table 2). To provide a more
comprehensive picture, we included an additional paper by Burton published in 2012 in
our review [
29
]. The studies we assessed were all retrospective and observational, except
for a literature review conducted by Samia et al. in 2019 [
30
], mostly undertaken in Kenya
and South Africa in cohorts ranging from 76 [31] to 2407 PWE [32].
A slight male predominance was observed in most studies, except for one that reported
a higher proportion of females. Regarding seizure classification, the 2017 International
League Against Epilepsy (ILAE) position papers’ suggestions were fully applied in its ex-
tended version only by Ackermann et al. and Aricòet al. [
32
,
33
]. The remaining papers uti-
lized less detailed classifications, sometimes combining seizure classification with epilepsy
and syndrome classification. Published studies exhibited a significant heterogeneity in
terms of seizure semiology, with varying percentages reported for different seizure types.
Focal seizures ranged from 8.2% to 77.7% in the descriptive articles, and from 13.1% to 78.6%
in the review article by Samia et al. Generalized motor seizures were often poorly defined,
but generalized tonic–clonic (GTC) seizures were commonly acknowledged across multiple
studies [
30
–
35
]. Myoclonic, tonic, atonic, and clonic seizures were reported in a limited num-
ber of papers [
29
,
31
–
34
], and epileptic spasms were mentioned in three studies [
32
,
33
,
36
].
Generalized nonmotor seizures (absence seizures) were cited in five papers [
29
,
32
–
34
,
37
],
while focal nonmotor seizures were mentioned in only
two studies
[
32
,
33
]. Awareness
during focal seizures was considered in five
articles [29,33–35]
. Regarding the classifi-
cation of epilepsy, in Sub-Saharan Africa, most epilepsies have been classified as focal
(50–65%), resembling the figures observed in HIC (60–70%). The definition of the type of
epilepsy rather than seizures is, however, more difficult and often requires a longitudinal
observation [4,12,22].
Most of the reviewed papers presented electroencephalogram (EEG) findings, with
varying rates of EEG abnormalities reported (20–89%). However, the classification of these
abnormalities differed remarkably, making it challenging to compare results. Few studies
included neuroimaging data, primarily consisting of CT scans, which provided additional
insights into the neuroradiological correlates of epilepsy.

J. Clin. Med. 2024,13, 6396 7 of 32
Table 2. Overview of articles reporting data on semeiology of epileptic seizure and classification. The table summarizes the data on clinical manifestations of seizures,
availability of diagnostic procedures (by EEG and CT or MRI scan) in different Sub-Saharan African countries. CWE = children with epilepsy, SeLECTS = Self-limited
epilepsy with centrotemporal spikes, DALYs = disability-adjusted life, PWE = people with epilepsy, CSE = convulsive status epilepticus,
ILAE = International
League Against Epilepsy, MRI = magnetic resonance imaging, EEG = electroencephalogram, CT = computerized tomography.
Scheme Primary Focus and
Population
Seizure/Epilepsy
Classification EEG Neuroimaging Limitations
Burton et al., 2012 [29]
Tanzania. Prevalence and risk
factors for epilepsy in
children: 112 CWE age 6–14 y
(males 50.9%).
- Focal motor onset with
secondary
generalization 73
(65.2%).
- Generalized motor
onset tonic–clonic and
clonic 19 (16.9%).
- Focal onset with
impaired awareness 11
(9.8%).
- Generalized motor
myoclonic 2 (1.8%)
- Focal motor 3 (2.7%).
- Generalized non motor
onset (typical) 1 (0.9%).
- Unclassified 3 (2.7%).
Performed in 101 patients.
- EEG anomalies in 44
patients (43.6%),
particularly:
- Generalized
epileptiform
abnormalities 9 (20.5%).
- Multifocal epileptiform
abnormalities 11 (25%).
- Temporal lobe
abnormalities 7 (15.9%).
- Extratemporal focal
abnormalities 9 (20.5%).
- Generalized
non-epileptiform
abnormalities 8 (18.1%).
CT performed in 90 patients
(80.3%).
Neuroradiological anomalies
in 26 patients (28.9%),
particularly:
-
Focal cerebral atrophy 5
(19.3%).
- Cerebellar/ brainstem
atrophy 4 (15.4%).
- Porencephalic cyst 2
(7.7%).
- Generalized lack of
white matter bulk 3
(11.5%).
- Calcified lesion 2
(7.7%).
- Neurocysticercosis 2
(7.7%).
- Pre/perinatal vascular
event 5 (19.3%).
- Previous tuberculous
meningitis 1 (3.8%).
- Sturge–Weber 1 (3.8%).
- Tuberous sclerosis 1
(3.8%).
- Small sample.
- No data for age groups.
- Seizure classification
rough.

J. Clin. Med. 2024,13, 6396 8 of 32
Table 2. Cont.
Scheme Primary Focus and
Population
Seizure/Epilepsy
Classification EEG Neuroimaging Limitations
Lagunju et al., 2015 [37]
Nigeria. EEG impact on
epilepsy care in children
referred to a pediatric
neurology clinic with
suspicion on epilepsy. CWE
329 age: 3 mos–16 y: males =
59.9%.
- Generalized onset 151
(48.7%).
- Focal onset 57 (18.4%).
- Focal onset with
secondary
generalization 47
(15.5%).
- Generalized nonmotor
onset (typical) 25 (8.1%).
- Infantile epileptic
spasm syndrome (IESS)
16 (5.2%).
- SeLECTS 10 (3.2%).
- Lennox–Gastaut
syndrome 2 (0.6%).
- Dravet syndrome 2
(0.6%).
Performed in 329 patients.
EEG anomalies in 108
(32.82%), particularly
-
Continuous generalized
slow wave activity 75
(69.4%).
- Diffuse slow wave
activity with a poorly
organized background
14 (13%).
- Asymmetry 11 (10.2%).
- Intermittent regional
slow wave activity 6
(5.6%).
- Beta waves 2 (1.8%).
Not performed.
- Epileptic syndromes
included into epilepsy
classification.
- No data for age groups.
- EEG findings imprecise.
- Seizure classification
rough.
Kariuki et al., 2024 [38]
Kenya. Determine incidence,
DALYs, risk factors and
causes of admissions in PWE
in a rural hospital. 743 CWE
age: 0–13 y, males = 60%.
- Generalized onset
seizures 646 (86.94%).
- Focal onset seizures 97
(13.1%).
- “Complex seizures”
(focal onset, prolonged
and/or repetitive) 427
(58%).
Not performed. Not performed.
- No diagnostic tools
used.
- No data for age groups.
- Seizure classification
rough.

J. Clin. Med. 2024,13, 6396 9 of 32
Table 2. Cont.
Scheme Primary Focus and
Population
Seizure/Epilepsy
Classification EEG Neuroimaging Limitations
Reddy et al., 2017 [31]
South Africa. Pediatric CSE.
76 CWE age: 1 mo–13 y,
males 62%.
- Generalized motor
tonic–clonic 40 (53%).
- Focal motor onset
seizures evolving in
CSE 14 (18%).
-
Generalized motor tonic
3 (4%)
- Unknown onset 19
(25%).
Performed in 44 (58%)
patients.
Findings:
- EEG anomalies in 39
(89%) Particularly:
- Epileptiform activity 4
(10%)
- Low amplitude pattern
4(10%)
- Electro-cerebral silence
4(10%)
- Burst suppression 3
(8%)
- Diffuse beta activity 1
(3%)
Performed in 70 (92%)
patients:
- MRI: 25 (36%) patients.
- CT: 68 (97%) patients.
Findings:
- Neuroradiological
anomalies 53 (76%),
particularly
- Hypoxia.
- Hypoperfusion-related
changes 17 (32%).
- Arterial infarct 7 (13%).
- Leptomeningeal
enhancement 6 (11%).
- Cerebral oedema 6
(11%).
-
Cerebral atrophy 5 (9%).
- Venous
thrombosis/venous
infarcts 4 (8%).
- Other abnormalities 8
(16%).
- Small sample.
- Incomplete
documentation for
some records.
- No data for age groups.
- Seizure classification
rough.
Matonda-ma-Nzuzi et al.,
2018 [36]
Congo. Behavioural
problems and cognitive
impairment in CWE
attending a mental health
center. 104 CWE age: 6–17 y,
males 58.6%.
- Focal onset seizures 58
(55.8%).
- Generalized onset
seizures 35 (33.6%).
- Generalized motor
epileptic spasms 3
(2.9%).
- Unclassified 8 (7.7%).
Not performed. Not performed.
- Small sample.
- No diagnostic tools
used.
- No data for age groups.
- Seizure classification
rough.

J. Clin. Med. 2024,13, 6396 10 of 32
Table 2. Cont.
Scheme Primary Focus and
Population
Seizure/Epilepsy
Classification EEG Neuroimaging Limitations
Lompo et al., 2018 [39]
Burkina Faso. Etiology of
nongenetic epilepsies in CWE.
115 CWE age 0–18 y, males
62.6%.
- Focal onset epilepsy 70
(60.9%).
-
Frontal onset 33 (28.7%).
- Central onset 15 (13%).
- Temporal onset 14
(12.2%).
- Occipital onset 8 (6.9%).
- Generalized onset
epilepsy 22 (19.1%).
- Focal onset to bilateral
tonic-clonic 13 (11.3%).
- Undetermined 10
(8.7%).
Epileptic paroxysmal
anomalies 86 (74%)
Performed:
- MRI: 11 (9.6%) patients.
- CT: 104 (90.4%)
patients.
Findings:
Neuroradiological anomalies
72 (62.2%), particularly
- Cortico-subcortical
atrophy 55 (47.8%).
- Circumscribed
hypodensity 18 (15.6%).
- Cortico-subcortical
calcifications 5 (4.3%).
- Porencephalic cavity 12
(10.3%).
- Chronic hydrocephalus
4 (3.5%).
- Heterogeneous nodules
under ependymal 2
(1.7%).
- Hippocampal sclerosis
3 (2.6%).
- Cortical development
malformations 3 (2.6%).
- Brain tumor 2 (1.7%).
- Small sample.
- No data for age groups.
- EEG findings imprecise.
- Seizure classification
rough.

J. Clin. Med. 2024,13, 6396 11 of 32
Table 2. Cont.
Scheme Primary Focus and
Population
Seizure/Epilepsy
Classification EEG Neuroimaging Limitations
Ahmad et al., 2018 [34]
Nigeria. Clinical seizure
types and EEG findings in
CWE seen in a pediatric
neurology clinic. 303 CWE
age: 3 mos–15 y, males 65.5%.
- Generalized motor
onset tonic–clonic
- 192 (63.4%).
- Generalized motor
onset myoclonic 31
(11.9%).
- Generalized motor
mixed forms 31 (10.2%).
- Focal onset to bilateral
tonic-clonic 18 (5.9%).
- Generalized motor
onset atonic 9 (3%).
- Focal motor onset 7
(2.3%).
- Generalized non motor
onset (typical) 3 (1%).
- Epileptic syndromes
7(2.3%).
Performed in 176 (58.1%)
patients.
Epileptiform discharges
found in 146 (83%) records.
Not performed.
- Old classification used.
- Epileptic syndromes
included into seizure
classification.
- No data for age groups.
- Seizure classification
rough.
- EEG findings imprecise.
Ackermann et al., 2019 [32]
South Africa. Epidemiology
of CWE referred to a tertiary
service. 2407 CWE age: 0–12,
males 56%.
Seizure types grouped by age
and more detailed
classification.
- Generalized onset 1056
(52%).
- Focal onset 1309 (54%).
- Unknown onset 244
(10%).
Not performed. Not performed. - No data from
diagnostic tool.

J. Clin. Med. 2024,13, 6396 12 of 32
Table 2. Cont.
Scheme Primary Focus and
Population
Seizure/Epilepsy
Classification EEG Neuroimaging Limitations
Egesa et al., 2022 [35]
Kenya. To Review seizure
semiology and etiological
data to fit ILAE-2017 criteria.
256 CWE, males 43.2%.
Seizure type:
- Focal onset 299 (61.9%).
- Generalized onset 157
(32.5%).
- Unknown onset 27
(2.6%).
- Seizure subtypes:
- Generalized motor
onset tonic–clonic 31
(44.9%).
- Focal aware onset 42
(46.7%).
- Focal impaired aware
onset 57 (62%).
- Focal to bilateral
tonic-clonic 42 (47.2%).
Performed.
EEG anomalies 122 (60.1%).
Performed in 22% of the
whole sample. No data on
results.
- Retrospective analysis.
- No data for age groups.
- Seizure classification
rough.
- EEG findings imprecise.
Samia et al., 2022 [9]Childhood epilepsy care in
Kenya and knowledge gap.
- Generalized motor
onset tonic–clonic
33.6–70.4%.
- Focal onset
13.1%–78.6%.
Any abnormality 20–39%.
- Focal abnormalities up
to 61.6% of abnormal
EEGs.
- 3 Hz spike-wave 7.4%
of abnormal EEGs.
- Hypsarrhythmia 2.8%
of abnormal EEGs.
One study of neuroimaging
included.
No abnormal findings on 11
children with focal epilepsy
and loss of awareness.
- No data for age groups.
- Seizure classification
rough.
- EEG findings imprecise.

J. Clin. Med. 2024,13, 6396 13 of 32
Table 2. Cont.
Scheme Primary Focus and
Population
Seizure/Epilepsy
Classification EEG Neuroimaging Limitations
Aricòet al., 2023 [33]
Impact of a newly established
clinic for pediatric epilepsy.
143 CWE age 0–18; males
57.3%.
Seizure type:
- Generalized motor
onset tonic 87%.
- Generalized motor
onset clonic = 82%.
- Generalized motor
onset tonic-clonic 29%.
- Focal motor onset
automatism 14%.
- Generalized motor
onset myoclonic 10%.
- Generalized non motor
onset (cognitive, atonic,
absences, behavioural
arrest, epileptic spasms,
sensory): reported in
less than 10% of cases.
Epilepsy classification:
- Focal with motor onset
and impaired
awareness 51%.
- Motor generalized 24%.
- Focal with motor onset
and preserved
awareness 8%.
- Focal with nonmotor
onset and impaired
awareness 6%.
- Motor with unknown
onset 5%.
- Non motor generalized
(CAE) 3%.
EEG performed on 48 cases.
Findings:
- Normal EEG 9 (18.7%)
records.
- Background
abnormalities 27
records.
- Interictal abnormalities
34 records.
- Ictal abnormalities 8
records (5 focal, 3
diffuse).
- Focal abnormalities
(ictal or interictal) 19
(39.6%) records.
- Multifocal
abnormalities (ictal or
interictal) 9 (18.7%)
records.
- Diffuse abnormalities
(ictal or interictal) 7
(14.58%) records.
- EEG led to diagnosis
changes in 29.2% of
patients and to
treatment switch in
31.2% of patients.
Not performed.
- Retrospective analysis.
- Small sample.
- No data for age groups.

J. Clin. Med. 2024,13, 6396 14 of 32
3.4. Etiology
Epilepsy is a symptom of an underlying neurologic disease; indeed, the etiology of
epilepsy is a major determinant of clinical course and prognosis [
40
]. The new classification
of epilepsies from ILAE 2017 incorporates etiology along each stage of diagnosis, as it often
carries significant treatment implications. The new classification recognizes six etiological
subgroups, selected because of their potential therapeutic consequences: structural, genetic,
infectious, metabolic, immune, and unknown groups [41].
The etiological profile of epilepsy in SSA significantly diverges from HIC. There is a
higher prevalence of structural causes, possibly reflecting a greater burden from trauma
and brain infections, as well as a marked increase in infectious causes influenced by
endemic diseases.
Determining the causes of epilepsy typically demands the use of various diagnostic
tools like magnetic resonance imaging (MRI), EEG, genetic tests, and metabolic assessments.
Unfortunately, these resources are often scarce in Sub-Saharan Africa, limiting the chance
of obtaining conclusive data. Parasitic diseases (malaria cysticercosis, onchocerciasis, toxo-
cariasis, and toxoplasmosis), perinatal events, head injuries, HIV infection, and hereditary
factors can all be relevant provocative agents [
42
]. In 2014, Ba-Diop et al. published a
comprehensive review on Lancet neurology on epidemiology, causes, and treatment of
epilepsy in SSA, identifying family history of seizures, previous febrile seizures, perinatal
trauma, head injury, and central nervous system (CNS) infections as main risk factors [
43
].
After that, some national-based studies in SSA were published. We found 11 particularly
relevant studies (Table 3). Overall, structural or infectious etiologies appear to play a major
role in Africa [
30
,
35
,
39
,
42
,
44
]. Specifically, structural causes readily include the sequelae
of adverse perinatal events or cranial trauma [
39
], while infectious causes encompass a
former history of meningitis, cerebral malaria, or exposure to specific parasites [
30
,
45
,
46
].
A growing body of epidemiological research indicates that onchocerciasis may induce
seizures through direct or indirect mechanisms, giving rise to the concept of onchocerciasis-
associated epilepsy (i.e., nodding syndrome, see below) in affected areas [
47
,
48
]. Of note,
this has been highlighted as a significant but overlooked public health crisis, especially in
Sub-Saharan Africa, during the 2nd International Workshop on onchocerciasis-associated
epilepsies (OAEs) in Antwerp, Belgium, September 2023 [
49
]. A large amount of data
suggest a strong association between onchocerciasis and epilepsy—especially regarding
O. volvulus and higher microfilarial loads. Treating onchocerciasis by ivermectin also
reduces the seizure burden [
50
–
53
]. A recent brain MRI study performed in Kenyans and
South Africans with active convulsive epilepsy revealed structural abnormalities in 59–65%,
mostly attributable to hippocampal sclerosis and gliosis [
38
]. Apolot et al. had formerly
described similar figures in Uganda, also disclosing a correlation between the presence of
abnormal EEG findings and diagnosis of morphological brain abnormalities [54].

J. Clin. Med. 2024,13, 6396 15 of 32
Table 3. Etiology of epilepsy in Sub-Saharan Africa. The table shows an overview of the different causes of epilepsy. Structural causes and infectious etiologies
appear to be the most common in the Sub-Saharan African population. ACE = acute convulsive epilepsy, CWE = children with epilepsy DEE = developmental
and epileptic encephalopathies, MRI = magnetic resonance imaging,
PWE = people
with epilepsy, HS = hippocampal sclerosis, OAEs = onchocerciasis-associated
epilepsies, Ov = Onchocerca volvulus, CNS = central nervous system.
Study Population Type of Study Main Findings
Ngugi et al., 2013 [42]South Africa, Ghana, Kenya,
Tanzania, Uganda.
Observational cross-sectional,
case–control.
Risk factors for active convulsive epilepsy in children (aged < 18 y) (p< 0.0001): seizure in
the family; abnormal antenatal period; difficulties feeding, crying, or breathing; any other
problems after birth.
Kamuyu et al., 2014 [45]South Africa, Ghana, Kenya,
Tanzania, Uganda.
Observational cross-sectional,
case–control.
Association between individual parasites (O. volvulus, T. canis and T. gondii) and ACE
prevalence.
Greater combined effect for coinfection with T. gondii and O. volvulus.
Christensen et al., 2015 [46]Malawi, Kenya, Uganda,
Gabon, Mali. Review. Cerebral malaria is associated with an increased risk of epilepsy as a long-term adverse
outcome (OR 4.68, 95% CI 2.52–8.70).
Lompo et al., 2018 [39] Burkina Faso. Observational
cross-sectional.
Main etiologies among nongenetic epilepsies:
- Neurocutaneous syndrome 1.7%.
- Malformation of cortical development 2.6%.
- Sequelae of cranial and brain trauma 5.6%.
- Sequelae of central nervous system infection 29.6%.
- Brain tumors 1.7%.
- Sequelae of perinatal cerebral suffering 34.8%.
- Hippocampal sclerosis 1.7%.
Samia et al., 2019 [30] Kenya. Review. Common risk factors in children for both epilepsy and acute seizures included adverse
perinatal events, meningitis, malaria, febrile seizures, and family history of epilepsy.
Sahlu et al., 2019 [55] Burkina Faso. Randomized, case–control. Positive association between seropositivity to cysticercal antigens and active epilepsy
(prevalence odds ratio: 2.40 (95% CI: 1.15–5.00)).
Egesa et al., 2022 [35] Kenya. Review.
The most common etiologies of epilepsy: infectious (44.8%) and structural (36.4%).
Structural causes were higher in CWE (44.9%) than in adults (26.9%), (p< 0.001).
About 24.6% of persons had undetermined epilepsy causes.
Essajee et al., 2022 [56] South Africa. Observational prospective.
A genetic underlying cause for DEE was identified in 18 of 41 CWE (diagnostic yield
43.9%) by performing a targeted next generation sequencing analysis. The more common
pathogenic variants were found in SCN1A (n = 7), KANSL1 (n = 2), KCNQ2 (n = 2) and
CDKL5 (n = 2).

J. Clin. Med. 2024,13, 6396 16 of 32
Table 3. Cont.
Study Population Type of Study Main Findings
Apolot et al., 2022 [54] Uganda. Observational cross-sectional.
The prevalence of structural abnormalities among CWE was 74.15%. Acquired structural
brain abnormalities were the commonest at 69.22% with hippocampal sclerosis (HS)
leading while disorders of cortical development were the most common congenital causes.
Mazumder et al., 2022 [51] Uganda. Observational longitudinal,
case–control.
Comparison between structural changes in the brain MRI between nodding syndrome and
other forms of OAE; relation between structural changes to the OV-induced immune
responses and level of disability. Treatment of onchocerciasis reduces the seizure burden.
Siewe Fodjo et al., 2022 [53] Cameroon. Observational longitudinal.
Documented ongoing transmission of onchocerciasis alongside a suboptimal ivermectin
coverage: the patients with epilepsy were more Ov-infected than participants without
epilepsy, supporting the existence of an association between onchocerciasis and epilepsy.
Having O. volvulus infection and especially higher microfilarial loads was significantly
associated with epilepsy.
Esterhuizen et al., 2023 [57] South Africa. Observational longitudinal.
Tested genetically 234 naive South African children diagnosed with/possible DEE: 41 (of
234) children with likely/pathogenic variants, 26 had variants supporting precision
therapy. Importance of early genetic diagnosis in DEE. We designed the “Think-Genetics”
strategy for early recognition, appropriate interim management, and genetic testing for
DEE in resource-constrained settings.
Bhattacharyya et al., 2023 [48] South Sudan. Diagnostic/prognostic.
Development of a mathematical model to quantified transmission, disease parameters and
predict the impact of ivermectin mass drug administration (MDA) and vector control. The
model estimated an OAE prevalence of 4.1% in Maridi County. The OAE incidence is
expected to rapidly decrease by >50% within the first five years of implementing annual
MDA with good coverage (
≥
70%). With vector control at a high efficacy level (around 80%
reduction in blackfly biting rates) as the sole strategy, the reduction is slower, requiring
about 10 years to halve the OAE incidence. Increasing the efficacy levels of vector control,
simultaneously with MDA, yielded better results in preventing new cases of OAE.
Edridge et al., 2023 [44]
Uganda, Malawi, and Rwanda.
Observational.
Viral and bacterial CNS infections and IMDs are prevalent causes of severe acute
encephalopathy in children in Uganda, Malawi, and Rwanda. These causes are likely to be
missed by conventional diagnostics and are associated with poor outcome of disease.
Jada et al., 2023 [47] Sudan. Longitudinal,
population-based.
Onchocerciasis may induce seizures through direct or indirect mechanisms: strengthening
onchocerciasis elimination interventions can decrease the incidence of epilepsy, including
nodding syndrome.

J. Clin. Med. 2024,13, 6396 17 of 32
Table 3. Cont.
Study Population Type of Study Main Findings
Kariuki et al., 2024 [38] Kenya and South Africa. Observational retrospective.
MRI abnormalities were found in 140 of 240 of PWE in Kenya, and in 62 of 91 in South
Africa (pooled modeled prevalence = 61%) Abnormalities were common in those with a
history of adverse perinatal events (65%, exposure to parasitic infections (69%) and focal
electroencephalographic features (68%), 95% CI: 60%–76%). Mesial temporal sclerosis
(43%) and gliosis (34%) were the most frequent abnormalities found.
Colebunders et al., 2024 [49] Sub-Saharan Africa. Review.
Underline the strong association between onchocerciasis and seizures, reinforcing the
concept of OAE; need for case definition to estimate the burden of disease and identify
onchocerciasis-endemic areas requiring intensification of elimination programs and
integration of epilepsy care. To reduce OAE burden, enhance collaboration with mental
health programs at community, national, and international levels is required.
Amaral et al., 2024 [52] Sudan. Observational prospective.
Observed decrease in epilepsy incidence despite suboptimal cumulative
community-directed treatment with ivermectin coverage highlights the potential impact of
onchocerciasis control efforts and underscores the need to strengthen these efforts.

J. Clin. Med. 2024,13, 6396 18 of 32
However, these findings may not fully represent the actual spectrum of epilepsy-
inducing conditions in Africa, but, rather, the diagnostic opportunities available. In the
past decade, no data on genetic or metabolic epilepsies in SSA were published until 2022.
Since then, two prospective studies employing molecular testing on a cohort of patients
with developmental and epileptic encephalopathies (DEE) have been performed in South
Africa. Essajee et al. revealed a noteworthy diagnostic yield of next-generation sequencing
(NGS) analysis, identifying pathogenic variants in 18/41 (43.9%) patients by a panel of
308 genes [
56
]. Esterhuizen et al. analyzed a cohort of children with DEE by means not only
of a gene panel built on 71 DEE-associated genes, but also by chromosomal microarray and
exome sequencing. They found pathogenic variants in 41/234 subjects (19%), especially
in those with neonatal/early infantile onset, neuropsychiatric comorbidities, and somatic
dysmorphisms. In these high-risk subjects, the authors opted for genetic investigations
based on a “Think-Genetics” decision tree, which is particularly suited to low-income
settings. The first level of analysis involved small gene panels or chromosomal microarrays,
with the latter reserved for those with a history of intellectual disability or dysmorphisms.
Only unresolved cases were subjected to exome sequencing, a technique accessible to only
a fraction of patients in Sub-Saharan Africa. Of the 41 children with pathogenic/likely
pathogenic findings, 26 had variants with treatment implications [
57
]. Those studies
revealed a noteworthy diagnostic yield of genetics, suggesting that genetic epilepsies are
consistently underdiagnosed in SSA.
3.5. Nodding Syndrome
In recent years, there has been growing interest in an acquired neurological disorder
called nodding syndrome (NS), characterized primarily by severe attacks of nodding of
the head, followed by behavior difficulties and psychiatric disorders, declining cognitive
function, stunting and growth failure, delayed puberty, and physical and motor disabil-
ity [
58
,
59
]. NS commonly appears in children aged 5 to 15 years old [
60
], often following
prodromal symptoms observed two years prior to the onset of head nodding. These early
signs include periods of blank staring, inattentiveness, complaints of dizziness, lethargy,
and general weakness [
58
]. As Abd-Elfarag et al. point out in their systematic review,
nodding syndrome is a severe neurological disease, and while its precise cause is still
under investigation, studies have explored various factors such as infections, autoimmune
responses, and nutritional deficiencies [61].
During a nodding episode, a sudden loss of muscle tone occurs, causing the head to
drop forward toward the chest. This happens at a rate of about 5–10 drops per minute.
Ictal EEG shows generalized electrodecrement, and paraspinal electromyography indicates
a dropout consistent with an atonic seizure [
62
]. The head nod represents the main and
most characteristic symptom of the condition. However, patients frequently experience
concurrent myoclonic jerks and atypical absences and may develop additional seizure
types over time, including tonic–clonic and myoclonic seizures [
58
]. The condition usu-
ally progresses with cognitive decline, behavioral disturbances, especially learning and
memory difficulties, temper tantrums, and depression. Some patients may develop limb
deformities and spine abnormalities [
58
]. Brain MRI studies showed varying degrees of
cortical and cerebellar atrophy, along with frontal subcortical gliosis in some patients as
well as hippocampal atrophy and sclerosis [60].
NS treatment includes antiseizure medications, nutritional support, and psychosocial
interventions to manage symptoms and improve quality of life. Epilepsy prognosis is
quite poor. Seizures are usually managed with common ASMs, such as sodium valproate,
carbamazepine, phenytoin, and phenobarbital, leading to seizure freedom in 0–25% of
cases [
60
,
63
]. A recent cross-sectional observational study has indicated that phenytoin may
be more effective in controlling head nodding compared to monotherapy with other ASMs.
However, these findings necessitate further validation through additional research [64].
The cause of NS is still unknown, but several factors have been proposed both as
causative or predisposing: (i) Infections: There is a strong relationship between nodding

J. Clin. Med. 2024,13, 6396 19 of 32
syndrome and infection with the parasite Onchocerca volvulus. This is supported by
several observations: no cases of nodding syndrome have been found in areas not en-
demic for O. volvulus [
60
]. A higher rate of infection with O. volvulus was found in
PWE compared to nonepileptic controls, O. volvulus was identified as a predictor of
epilepsy later in life, and successful onchocerciasis elimination strategies have reduced
the incidence of epilepsy in regions endemic for onchocerciasis [
65
]. Despite that, the
microfilaria in the CNS are exceedingly rare and there is no documented incidence of
O. volvulus in brain tissue [
60
]. (ii) Autoimmune response: It has been proposed that
O. volvulus infection could trigger neuroinflammation and neurotoxicity by an immune-
mediated response. Particularly, a strong cross-reactivity was found between Leiomodin-1
antibodies (an action-binding protein increased in patients with NS) and O. volvulus
antigens, creating a cycle of injury and neuroinflammation [
60
]. (iii) Malnutrition: Vita-
min B6 deficiency was found to be a main risk factor for NS [
66
]. In families with one
or more NS cases, a history of shortage and consumption of moldy maize was notably
more prevalent before the onset of head nodding [
67
]. (iv) Genetics: An association was
found between NS and both protective HLA haplotype (HLA-B*42:01, C*17:01, DRB1*03:02,
DQB1*04:02 and DQA1*04:01), and susceptible motif (Ala24, Glu63 and Phe67), in the HLA-
B peptide-binding groove. Those findings suggest that immunogenetic fingerprints in HLA
peptide-binding grooves tentatively associate with protection or susceptibility to NS [
59
].
(v) Neurodegenerative condition: There is speculation that NS could represent a form
of tauopathy since postmortem studies revealed filamentous tau-positive deposits in the
neocortex, in the locus coeruleus, in the substantia nigra, and tegmental nuclei, and since
neurological decline is observed in most patients [68].
NS represents an enigmatic and intricate condition characterized by the onset of
epilepsy in childhood and a progressive neurological decline. Its etiology involves a multi-
faceted interplay of factors. Notably, NS presents distinctive traits aligning it with DEE,
a heterogeneous group of conditions characterized by early-onset severe epilepsy, EEG
abnormalities, and developmental impairment that tends to worsen as a consequence
of epilepsy [
41
]. Indeed, as observed by Mazumder et al., NS shares EEG features with
late-onset spasms and Lennox–Gastaut syndrome such as ictal slow waves followed by
electrodecrement responses and ictal cortical gamma rhythms, suggesting involvement of
widespread epileptic networks across cortical and subcortical structures [
53
]. Given the
age of onset, the progressive clinical trajectory, and distinctive electroencephalographic
features, it is plausible to categorize NS as a novel variant of DEE, warranting a multidisci-
plinary approach to its management. On the other side, a recent autoptic study performed
in Uganda has revealed tau pathology in NS, with a peculiar pattern of superficial corti-
cal accumulation, largely involving gyral crowns, that allows distinction from the other
tauopathies. The cause of the tau pathology in NS has not yet been established [68].
3.6. HIV-Related Epilepsy
Children under 15 years of age with HIV infection are estimated to be 2.6 million
worldwide, and the greater part lives in LAMICs (primarily Sub-Saharan Africa and
Southeast Asia) [
69
]. NeuroAIDS is a complication of HIV infection, and the term refers
to the spectrum of central and peripheral nervous system effects caused by the virus.
Neurological complications in children can be either a direct consequence of HIV infection
(such as neuronal damage, cell death) or of secondary conditions (opportunistic infections,
cerebrovascular disease, malignancies) [
69
], or they can result from the indirect effects of
HIV including social stressors, poverty, illness, and trauma [
70
]. Epilepsy and seizure are
among the most frequent CNS complications of HIV infection. At the moment, the precise
prevalence of epilepsy in children with HIV infection in Africa is not clear; according to [
69
],
it is 7.6–14%. It is possible that many regional differences, partially related to the risk of
becoming infected, the availability of antiretroviral therapy (ART) and ASMs, make the
evaluation difficult. From 2013 to 2023, there were six papers regarding epilepsy in patients
with HIV infection/AIDS in Africa (five original research and a chapter taken from the

J. Clin. Med. 2024,13, 6396 20 of 32
Handbook of Clinical Neurology). All the other original research was either longitudinal
or retrospective observational studies, including from 29 to 2137 subjects according to
the inclusion criteria (e.g., HIV-infected children, HIV-infected children with new-onset
seizure) (Table 4). All the data derive from SSA countries (Zambia, South Africa, Uganda,
Botswana). Most studies had a slight male predominance. Different aspects of epilepsy in
HIV-infected children have been explored, ranging from the clinical profiles of HIV disease
in children to the prevalence of epilepsy (and other neurological disorders) in HIV-infected
children and correlation with being on ART.
According to the semiology, there was a predominance of generalized tonic–clonic
seizures (51–67.3%); status epilepticus was commonly reported (21.2% according to Bur-
man et al. [
71
], 37% according to Ravishankar et al. [
72
]). The most common etiologies
for epilepsy were CNS infections (opportunistic and nonopportunistic) followed by HIV
neurotoxicity, structural lesions, metabolic disturbances, and birth asphyxia. According
to the WHO stage of HIV disease, 60–76% of CWE were in an advanced stage of the dis-
ease (WHO stage 3 or 4), with the exception of one study [
70
], in which the majority of
participants (55.7%) were on WHO stage 2. There was great variability in the diagnostic
evaluation. Neuroimaging (CT scan and/or MRI) was more likely performed in children
with HIV disease and epilepsy compared to children with no epilepsy, but these opportuni-
ties were mainly available in urban hospitals where there was the possibility of obtaining an
EEG recording. Antiepileptic treatment was investigated in only two papers [
71
,
73
]. Both
assessed that sodium valproate was the most frequently ASM used. Seizure control was
investigated in only one paper and it emerged that 24 out of 49 patients became seizure-free
while 8 out of 49 patients had significant reduction in seizure frequency. Burman et al.
investigated the possible interactions between ASMs and ART (specifically Efavirenz) that
may have influenced the seizure control. It ended up that children with poor control of
their seizures were more likely treated with Efavirenz, which is an inhibitor and inducer of
CYP3A4, a crucial enzyme in the ASMs metabolism [
71
]. Surprisingly, former studies had
shown that EFV has no effect on the metabolism of ASMs. Further investigations regarding
responsibility of drug interactions on seizure control are needed.
In conclusion, all the reviewed papers agreed that epilepsy is a common neurologic
complication of HIV infection, that more likely affects [
74
] children in advanced stage
of disease and that can worsen the prognosis. In one reviewed paper [
73
], 75% of the
children enrolled were diagnosed with epilepsy before or when starting the ART; this
suggests that the presence of clinical manifestations of epilepsy could have caused further
investigations and accelerated the disclosure of an HIV-infection. Bearden et al. assessed
that being on early treatment with combined antiretroviral therapy (cART) can reduce
the odds of epilepsy by reducing the rates of CNS infections and HIV neurotoxicity [
75
].
Therefore, although the optimal timing for starting cART in LAMICs is still unknown,
early treatment appears to be protective against neurological complications and, indirectly,
against epilepsy itself.

J. Clin. Med. 2024,13, 6396 21 of 32
Table 4. Associations of HIV infection and seizures. Overview of the articles reporting data on epilepsy in children with HIV infections comparing the epidemiology,
etiology, and characteristics of the used medications. HIV = human immunodeficiency virus, CT = computed tomography,
MRI = magnetic
resonance imaging,
EEG = electroencephalogram
, CWE = children with epilepsy, CNS = central nervous system, WHO = World Health Organization, ART = antiretroviral therapy,
CSF = cerebrospinal
fluid, ASMs = antiseizures medications, VPA = valproic acid, LTG = lamotrigine, LEV = levetiracetam, LCM = lacosamide, GBP = gabapentin,
PGB = pregabalin, GTC = generalized tonic–clonic, TB = tuberculosis.
Study Population Study Design Seizure/Epilepsy
Classification
Diagnostic
Evaluation Etiology HIV WHO Stage ART and/or ASMs Main Findings
Bearden et al.,
2015 [76]
Botswana; 29 HIV
CWE aged 0–18
years and 58
matched controls.
Observational
retrospective,
case–control.
Not mentioned.
- Cranial CT: 20.
- Brain MRI: 4.
- CSF: 15.
- EEG not
available.
- CNS infections
(tuberculosis
meningitis,
cryptococcal
meningitis, bacterial
meningitis,
toxoplasmosis) 31%.
- HIV neurotoxicity
27%.
- Unknown 31%.
- Other (ischemic
stroke, congenital
malformation, birth
asphyxia) 9%.
At enrollment:
Cases WHO stage 4
66%. Controls WHO
stage 4 38%.
All participants on
cART during the
study (median age
70 months for both
case and controls).
39 patients (45%)
received early
treatment (8 cases
and 31 controls).
Not mentioned
ASMs.
Early treatment with
cART is likely to be
protective against
epilepsy in children
with HIV.
Wilmshurst J.M.
et al., 2018;
Chapter 8 of the
Handbook of
Neurology [71]
Children <15 years
in Sub-Saharan
Africa.
Review.
Focal onset seizures
are more likely than
generalized ones.
- Clinical
assessment.
- Laboratory
investigations.
- Chest X-ray.
- Cranial
CT—CSF.
May be related to HIV
damage or secondary to
acquired pathology
(neuroinfection).
Not mentioned.
- ASMs is often
limited.
- Drug–drug
interactions
with cART.
- VPA, LTG,
LEV, LCM,
GBP, PBG are
the favored
ASMs. VPA
and LTG are
the first-line
choice, LEV is
an alternative.
Main features of
epilepsy in HIV
patients.

J. Clin. Med. 2024,13, 6396 22 of 32
Table 4. Cont.
Study Population Study Design Seizure/Epilepsy
Classification
Diagnostic
Evaluation Etiology HIV WHO Stage ART and/or ASMs Main Findings
Mpango et al.,
2019 [72]
Uganda; 1070
participants: 677
(63.3%) aged
5–11 years and 393
(36.7%)
adolescents aged
12–17 years (48%
males).
43 (4%) with
probable epilepsy.
Observational
longitudinal. Not mentioned. Not mentioned. Not mentioned. 596 participants
(55.7%): stage 2.
1024 (95.7%): on
ART.
Not mentioned
ASMs.
Prevalence of
neurological
disorders (enure-
sis/encopresis,
motor or vocal tics,
epilepsy) among
children with HIV
was 18.5%.
Prevalence of
probable epilepsy
was 4%.
Burman et al.,
2019 [73]
South Africa; 227
participants
(10–176 months),
131 males (57.7%);
23% at least one
seizure, 14.2%
diagnosis of
epilepsy.
Observational
retrospective,
case–control.
- Generalized
seizures 35
CWE (67.3%;
most frequent:
GTC).
- Status
epilepticus 11
CWE (21.2%).
- Focal seizures
17 CWE
(32.7%).
- EEG 63.5%
had 56%.
- Brain scan:
100% in the
seizure’s
group more
likely to have
CT (69.4%)
than MRI
(44.6%).
- CNS infections
61.5%.
- Unknown 28.8%.
- Structural 9.6%.
69%: stage 4.
- 98% on ART
(median age
ART starting:
18 months).
- 53% were
treated with
VPA.
- Data on the
epidemiology
and
complexity of
management
of seizures in
HIV-infected
children.
- No correlation
between stage
disease and
seizure
occurrence.
- No correlation
between being
on ART and
age when ART
was started
with seizure
occurrence.
- Interactions
between
efavirenz and
ASMs are
unlikely to be
responsible for
poor seizure
control).

J. Clin. Med. 2024,13, 6396 23 of 32
Table 4. Cont.
Study Population Study Design Seizure/Epilepsy
Classification
Diagnostic
Evaluation Etiology HIV WHO Stage ART and/or ASMs Main Findings
Michaelis et al.,
2020 [75]
South Africa
(Eastern Cape)
2137 HIV children
(1 month–12 years).
53 (2.5%) with
epilepsy; 26 (53%)
males.
Observational
retrospective
study.
Not mentioned. Not mentioned.
Most common: prior CNS
infection (tuberculosis
meningitis).
- 76% of CWE:
WHO stage 3
or 4.
- 80% of
children
without
epilepsy:
WHO stage 1.
- 100% started
ART during
the study.
- 75%
diagnosed
with epilepsy
before ART.
- 48 out of 49
CWE were
treated with
VPA (24/49
became
seizure free,
8/49
significant
reduction in
seizure
frequency).
- Epilepsy
prevalence in
children with
HIV on ART
in a semirural
area was 2.5%.
- Prior CNS
infections
and/or HIV
encephalopa-
thy and
advanced
disease were
associated.
Ravishankar et al.,
2022 [74]
Zambia; 73
children (2.2–10
years) with HIV
infection and
new-onset seizure;
39 males (53%).
Observational
longitudinal.
- Focal seizures
36 (49%).
- Multiple
recurrent
seizures 28
(38%).
- Status
epilepticus 27
(37%).
-
Neuroimaging
(39 children).
- EEG (12
children).
- Infectious 54%
(opportunistic and
nonopportunistic
infections).
-
Metabolic 19% (renal
failure,
hypoglycemia).
- Structural lesions
10%.
44 (60%): WHO
stage 4.
36 (49%) were on
ART regimen (34 on
cART); of these, 19
children (56%) on
treatment for >1 year.
Not mentioned
ASMs.
- Despite
widespread
HIV testing
and cART in
Zambia, this is
not sufficient.
- New-onset
seizure in
children with
HIV occur in
advanced,
active HIV
disease.
- 22 children
(30%) died
due to
advanced HIV,
meningitis,
sepsis,
disseminated
TB, status
epilepticus.

J. Clin. Med. 2024,13, 6396 24 of 32
3.7. Diagnostic Tools
Regarding the diagnostic tools developed and validated in the African population
for the investigation of epilepsy, in the selected 10 years’ time frame, five articles were
reviewed in this article: on the development and validation of diagnostic questionnaires
(
n=3
, Table 5and Supplementary Material), on the impact of screening tools in low-
resource countries (n = 1), and on the access to electrophysiology services (n = 1).
The limited availability of laboratory, electroencephalography, and neuroimaging
testing mandates us to especially rely on history taking and surveys. Electroencephalog-
raphy (EEG) is available in various parts of Sub-Saharan Africa, but its accessibility and
availability can vary significantly between urban and rural areas. The cost of EEG testing
can be a barrier for many patients, Regular maintenance and technical support for EEG
machines can be a challenge, affecting their operational availability. Similarly, CT and
MRI facilities are more commonly found in major urban hospitals and medical centers,
particularly in capital cities, often with prohibitive costs. Functional MRI is even more
difficult to obtain, limiting the possibility to develop efficacious programs for epilepsy
surgery [77].
Specific diagnostic questionnaires can be extremely useful, especially in rural areas.
In their study, Patel et al. proposed a diagnostic questionnaire validated on the pediatric
population (6 months to 18 years), in comparison with the other authors that validated
the questionnaire from 6 years of age. The tool comprises 18 total questions. The initial
questions, in conjunction with three subsequent questions, inquire about the occurrence of
potential epileptic episodes. In the event of a positive response to the initial four questions,
a diagnosis of epilepsy can be made, thereby indicating that the investigator can proceed
with the subsequent 14 questions. The objective of the questionnaire is both to identify CWE
(question 1) and to classify the type of seizure into either focal/multifocal seizure (ques-
tions 2–13) or generalized seizure (questions 14–15) [
76
]. Vergonjeanne et al. described two
decades of experience with the questionnaire for Investigation of Epilepsy in Tropical Coun-
tries (IENT) [
78
]. The IENT questionnaire includes nine sections ranging from anamnestic
data to clinical examination, including a section on etiological investigations and treatment.
The first two sections, “demographic data” and “screening”, can be filled by a nonmedical
investigator. Jones et al. developed a tool for the diagnosis of convulsive seizures based on
binary information administered through a smartphone application. The tool is designed to
direct the individual to the most appropriate clinician. A further objective is to assist health-
care professionals in monitoring patients via the application. The screening questionnaire
is composed of binary questions (yes or no) and the responses provide the probability and
classification (likely or unlikely) of convulsive epilepsy. Upon diagnosis, a clinical report is
generated, comprising anonymized metadata and questionnaire responses [
79
]. All three
studies used a two-step approach with a first step characterized by screening participants
randomly selected or identified via door-to-door visits with a few screening questions and
the administration of a questionnaire by nonmedical healthcare workers. In step two, all
individuals screened positive from the questionnaire were invited to be examined by a
neurologist. According to Shalu et al., prevalence estimates obtained from the two-stage
approach may be seriously biased due to the failure to consider the imperfect validity of
the tests, used in the first or second stage, or in both stages, leading to verification bias
and misclassification errors. To overcome biases, it is important to compare the collected
data with statistically adjusted ones, obtained according to statistical analysis such as the
Bayesian latent-class models [55].

J. Clin. Med. 2024,13, 6396 25 of 32
Table 5. Diagnostic questionnaires. Of the 5 articles reviewed regarding the diagnostic tools, the table shows an overview of the three describing the development
and validation of diagnostic questionnaires. SSA = Sub-Saharan Africa.
Study Population Type of Study Intervention Indicator of
Accuracy Outcome Strengths Limitations
Patel et al., 2016 [78]
Tanzania and
Zambia; 6 months to
18 years.
Observational
longitudinal.
Administered to
patient’s caregiver by
a nonmedical staff
member.
15 most
discriminating
features of semiology
characteristics.
Sensitivity of 78%
and positive
predictive value of
81.5%.
Discriminate focal
from generalized
seizures.
Translated into local
dialects.
- Difficulties
with precise
classification of
specific seizure
semiologies.
- Does not
include all
types of
epilepsy.
- Does not
include
questions on
concomitant
illness and
etiologies.
Vergonjeanne et al.,
2021 [79]
African population;
all ages.
Review and
observational
longitudinal.
Questionnaire for
investigation of
epilepsy in tropical
countries (IENT).
9 sections with a total
of 213 items
combining both
binary and open
answer.
The first two sections
can be filled by a
nonmedical
investigator.
The sensitivity and
specificity were
estimated to be 95.1%
(95% CI: 87.3–98.4%)
and 65.6% (95% CI:
57.5–72.9%),
respectively.
- Estimate
prevalence in
an area.
- Identify clinical
forms of
epilepsy
determine
etiologies.
- Describe
treatment.
Available in several
languages (French,
English, Spanish, and
Portuguese).
- Validated in
2000, need an
update
according to
the new
classification of
epilepsy.
- A semiological
support could
be added to
im-prove the
classification of
seizures and
epilepsy.

J. Clin. Med. 2024,13, 6396 26 of 32
Table 5. Cont.
Study Population Type of Study Intervention Indicator of
Accuracy Outcome Strengths Limitations
Jones et al., 2023 [55]
SSA; population over
6 years.
Observational
retrospective,
case–control.
Questionnaire for
community-based
healthcare workers.
8 binary questions.
Sensitivity, specificity,
and positive and
negative predictive
values were 97.5%
(93.7–99.3), 82.4%
(71.2–90.5), 92.9%
(87.9–96.3), and 93.3%
(83.8–98.2; Table 2).
Diagnosis of
convulsive epilepsy.
- Free app
Epilepsy
Diagnostic
Companion
(EDC).
- Facilitating
more
appropriate
onward referral
to a
neurologist.
- Convulsive
seizures only.
- Regional limits.
- Difficulties in
follow-up
participation.
- Selection bias.
- Prevalence bias.

J. Clin. Med. 2024,13, 6396 27 of 32
In their last study, Kander et al. investigated the access and the level of competence of
the practitioner of electrophysiology services in SSA, with a special focus on pediatric elec-
trophysiology. As gold standard, EEG study performed by a neurophysiology technologist
and interpreted by a specialist with formal training in epileptology can assist and enhance
the diagnosis, delineation of syndromes, and, therefore, the management of epilepsy. Ac-
cording to the study, in terms of pediatric EEGs, the survey could not address evidence for
improved care; nevertheless, most participants agreed that a viable training model would
be beneficial to improve diagnosis and management for pediatric patients [80].
Interestingly, the EPInA Study Group has recently developed and validated the
Epilepsy Diagnostic Companion, a predictive modeling app designed to confirm con-
vulsive epileptic seizures in individuals with suspected epilepsy. Tailored to specific
cultural and regional contexts, it offers a simple questionnaire that can be administered by
nonspecialist healthcare workers. This tool has the potential to significantly enhance early
diagnosis and subsequent care for PWE through iterative updates [79].
4. Future Challenges and Study Limitations
Sub-Saharan Africa faces a significant shortage of healthcare professionals, espe-
cially pediatric neurologists. Many SSA countries have fewer than 0.03 neurologists per
100,000 people
, compared to 4–8 per 100,000 in most developed countries. The shortage is
particularly severe in rural areas, where access to any form of specialized care is limited.
A 2017 report indicated that some countries in Sub-Saharan Africa, such as Malawi, have
fewer than five neurologists serving the entire country, while other countries like Liberia
and Sierra Leone have no practicing neurologists at all. Only a small percentage of these
neurologists specialize in pediatric neurology. The low ratio of neurologists is compounded
by a lack of other specialized healthcare workers such as pediatricians, nurses, and gen-
eral practitioners trained to manage epilepsy [
77
]. A partial support may be obtained by
telemedicine, especially for the interpretation of diagnostic exams performed locally and
interpreted by expertise outside the continent [
81
], and promising data exist for low-cost
portable EEGs [
82
]. Active epilepsy may also be difficult to treat for the treatment gap.
The only widely available antiseizure medication in most nations is phenobarbital, pheny-
toin, carbamazepine, and valproate, which are substantially more expensive. Moreover,
patients often struggle with adhering to treatment regimens because they may not fully
understand the need to take daily medication for a condition that only causes symptoms
intermittently [
81
]. We should also consider that the limitation in diagnostic resource may
lead to misdiagnosis of functional/dissociative seizures (formerly known as psychogenic
nonepileptic seizures) as epilepsy, and often both conditions may be attributed to supernat-
ural causes, such as witchcraft or spiritual possession leading patients to seek help from
traditional or religious healers rather than medical professionals [83,84].
Therefore, providing most medical resources for clinical assistance and scientific research
is a major effort, also considering that different regions have to face specific difficulties.
In comparison to LMICs in Asia and Northern Africa, people from SSA have to
face higher prevalence rates, and children have major difficulties in accessing healthcare
infrastructure and diagnostic tools [84,85].
The heterogeneity of available studies prompted us to perform a scoping review, lim-
ited to diagnosis and classification. We attempted to summarize systematic and anecdotal
data available in the literature. However, many issues remain to be systematically ad-
dressed. A more comprehensive view on therapeutic options, quality of life determinants,
and epilepsy socioeducation would be needed.
5. Conclusions
Both SSA and the global population exhibit similar underlying patterns in the preva-
lence of epilepsy, with higher rates observed in pediatric populations compared to adults.
However, the prevalence can be significantly higher in SSA, especially for higher rates of
infectious diseases, socioeconomic challenges, and limited access to healthcare services.

J. Clin. Med. 2024,13, 6396 28 of 32
Classification and diagnosis may be more difficult due to a lack of resources and diagnostic
tools, such as EEG and neuroimaging.
Epilepsy poses a major public health burden, especially in nations with limited re-
sources, and even more so in SSA. In this setting, infectious diseases and head injuries may
play a major etiological role; however, further research is necessary to better estimate the
contribution of genetic factors. Diagnosing and understanding the root cause of epilepsy is
difficult due to a lack of equipment and specialists. Proper management of epilepsy hinges
on precise semiotic and etiological diagnosis. However, our review reveals that in SSA,
epilepsy is often poorly defined in terms of semiotic features, and etiological classification
is commonly lacking. PWE also face significant social challenges due to stigma and limited
access to treatment, impacting their quality of life and straining healthcare systems.
The path forward involves developing culturally sensitive diagnostic tools, increasing
access to affordable medication and treatment plans, and educating the public to reduce
stigma and promote social inclusion for PWE. Additionally, further research is needed
to explore the unique causes of epilepsy in Africa, such as genetic and metabolic factors.
Public health strategies to prevent epilepsy, like reducing complications during childbirth
and head injuries, can also significantly improve the situation.
Supplementary Materials: The following supporting information can be downloaded at: https:
//www.mdpi.com/article/10.3390/jcm13216396/s1, Details of epidemiology and diagnostic tools.
References [86–89] are cited in the supplementary materials.
Author Contributions: Conceptualization, E.B. and S.D.N.; methodology, E.B.; software, E.B., S.D.N.,
L.B. and I.A.; formal analysis, E.B., S.D.N., L.B. and I.A.; investigation, E.B., S.D.N., L.B. and I.A.;
resources, E.B., S.D.N., L.B. and I.A.; data curation, E.B.; writing—original draft preparation, E.B.,
S.D.N., L.B. and I.A.; writing—review and editing, E.B., S.D.N., L.B. and I.A.; visualization and
supervision, E.B. and S.D.N.; project administration; funding acquisition, E.B. and S.D.N. All authors
have read and agreed to the published version of the manuscript.
Funding: This work has been partially supported by grant-RC and the 5X1000 voluntary contribu-
tions, Italian Ministry of Health.
Institutional Review Board Statement: This study was conducted in accordance with the Declaration
of Helsinki, and approved by the Ethics Committee of Hospital Meyer, Florence, Italy (protocol code
Ped-COMPASS-CQ, date of approval: 20 August 2022).
Informed Consent Statement: Informed consent was not necessary in the study.
Data Availability Statement: The data presented in this study are available on request from the
corresponding author.
Conflicts of Interest: The authors declare no conflicts of interest.
Abbreviations
WHO = World Health Organization; PWE = people with epilepsy; CWE = children with epilepsy;
LAMICs = low- and middle-income countries; HICs = high-income countries; SSA = Sub-Saharan
Africa; ASM = antiseizure medications; NS = Nodding syndrome; ART = antiretroviral therapy;
cART = combined antiretroviral therapy; DALYs = disability-adjusted life years; ILAE = International
League Against Epilepsy; SMR = standardized mortality ratio; DEE = developmental and epileptic
encephalopathies; NGS = next-generation sequencing; MRI = magnetic resonance imaging; CT =
computerized tomography; EEG = electroencephalogram; CNS = central nervous system.
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