**2.1 Classification of seizures**

In 2017, the ILAE released the most recent guidelines for classifying seizures and epilepsies [5, 6, 16, 17]. Seizure classification begins with the mode of onset, whether focal or generalized [16]; the onset may also be unknown if the patient/ caregiver does not recall the details of the initial seizure manifestations. Focal-onset seizures are further categorized into two depending on the state of consciousness during any part of the seizure: retained awareness versus impaired awareness (**Figure 1**) [16]. Irrespective of whether the onset is focal or generalized, seizures are grouped based on their physical manifestations as being motor (visible external movements) or non-motor (**Figure 1**). There is also a special group for focal

#### **Figure 1.**

*ILAE 2017 classification of seizure types (extended version) [16]* (used with permission)*.*

onset seizures which evolve to generalized seizures, known as focal to bilateral tonic-clonic seizures [16]. Of note, absence seizures are considered as generalized non-motor seizures [16]. However, in case some seizure descriptions do not appropriately fit into any of these categories, they can be considered as "unclassified".

#### **2.2 Classification of epilepsies**

For epilepsies, the classification starts with the seizure type [6], and the certainty that the nature of the seizure(s) justifies the diagnosis of epilepsy [4]. Patients who do not meet criteria for epilepsy (for example, a single seizure or repeated provoked seizures) should be classified as to a seizure type, but classification should stop there [5]. Once the epilepsy diagnosis is confirmed, the epilepsy type can be deduced as focal, generalized, combined generalized & focal, or unknown (**Figure 2**) [6]. The epilepsy type is decided mainly on clinical grounds, and the diagnosis may be supported by EEG findings [6]. The final (facultative) level in epilepsy classification is the epilepsy syndrome diagnosis; an epilepsy syndrome refers to a cluster of features incorporating seizure types, EEG results, and brain imaging features that tend to occur together [6]. Each epilepsy syndrome often has specific features such as age at onset and remission (where applicable), seizure triggers, diurnal variation, and sometimes prognosis. Distinctive co-morbidities such as intellectual and psychiatric abnormalities may also be associated with specific epilepsy syndromes, as has been observed with the nodding syndrome [18]. Other common epilepsy syndromes include: Childhood Absence Epilepsy, Juvenile Absence Epilepsy, Juvenile Myoclonic Epilepsy, and Generalized Tonic-Clonic Seizures Alone; these are all forms of idiopathic generalized epilepsies [6]. Classification of epilepsy into syndromes often has etiologic, prognostic, and treatment implications [6].

A new feature in the 2017 epilepsy classification is that it integrates an etiology component as well as co-morbidities in epilepsy (**Figure 2**). Six etiological axes were enumerated by the ILAE task force: structural, genetic, infectious, metabolic, *Definition, Classification, and Burden of Epilepsy DOI: http://dx.doi.org/10.5772/intechopen.93599*

#### **Figure 2.**

*ILAE framework for the classification of epilepsies [6]* (used with permission)*.*

immune, and unknown etiologies. Co-morbidities which should be considered on a case-by-case basis when diagnosing/classifying epilepsy include: intellectual decline, psychiatric and behavioral abnormalities, psychosocial problems, sleep disorders, and motor deficits [6].

#### **2.3 Epilepsy etiologies**

#### *2.3.1 Structural etiologies*

These are caused by structural brain abnormalities which have been shown to substantially increase the risk of developing epilepsy. These abnormalities are usually detectable by neuroimaging and in association with electroclinical assessments, lead to a reasonable inference that they are responsible for the enduring predisposition to unprovoked seizures [3, 6]. Structural etiologies could be primitive (for instance congenital malformations), or acquired (from a stroke, head trauma, infection, hypoxic-ischemic encephalopathy) [6].

#### *2.3.2 Genetic etiologies*

Epilepsy etiology is considered as genetic if there exists a specific disease-causing variant in a gene or copy number variant, believed to be the explanation for the observed epileptogenicity [5]. Of note, genetic mutations are not always inherited, as several epileptogenic de novo mutations have been identified [6]. The genetic alteration often causes a very heterogeneous phenotypic spectrum. A few genetic epilepsies identified to date include: the syndrome of Benign Familial Neonatal Epilepsy (KCNQ2 or KCNQ3 mutations) [19] and the Dravet syndrome (SCN1A mutations) [20].

#### *2.3.3 Infectious etiologies*

These are the most common preventable causes of epilepsy, particularly in sub-Saharan Africa [13, 21]. The concept of an infectious etiology is that the epilepsy

#### *Epilepsy - Update on Classification, Etiologies, Instrumental Diagnosis and Treatment*

directly results from a known infection in which seizures are a core symptom [6]; it is the persistence of these seizures even after resolution of the acute infection that is referred to as epilepsy of infectious origin. Common examples of infectious etiologies include neurocysticercosis, tuberculosis, HIV, cerebral malaria, subacute sclerosing panencephalitis, cerebral toxoplasmosis, and congenital infections such as Zika virus and cytomegalovirus [6, 22]. A recent cohort study supports the addition of onchocerciasis to this list, as the more infected participants had an increased risk of developing epilepsy later in life [23]. These infections sometimes have a structural correlate to explain the seizure recurrence even after anti-infectious treatment; this results in a substantial overlap with the acquired structural causes of epilepsy [5].

#### *2.3.4 Metabolic etiologies*

In some cases, the core cause of the epilepsy results from a metabolic derangement. Clinical entities such as porphyria, uremia, aminoacidopathies, or pyridoxine-dependent seizures all fall within this category. These conditions may also be associated with a pre-existing genetic defect, although a few can be acquired such as cerebral folate deficiency [6].

#### *2.3.5 Immune etiologies*

There are a rising number of persons in whom the epilepsy is caused by an autoimmune condition, as evidenced by an autoimmune-mediated central nervous system inflammation [6]. Examples include anti-NMDA (N-methyl-D-aspartate) receptor encephalitis and anti-LGI1 encephalitis [24]. The antileimodin antibodies hypothesis for central nervous system damage would equally place Nodding syndrome in this category [25].

#### *2.3.6 Unknown etiology*

For many PWE, the exact etiology may not be known. In such cases, diagnosis and management are solely based on electroclinical findings [6]. Nevertheless in some settings, epidemiological observations may provide clues as to a possible epilepsy etiology within a given vicinity. For instance, a pooled analysis of 37 studies showed that the etiologic fraction of epilepsy was estimated to be 63.0% (95% CI: 61.4 ± 64.5) in persons exposed to cysticercosis [26]. Therefore, in cysticercosisendemic settings, it would be reasonable to assume that a considerable number of epilepsy cases are due to neurological complications of *Taenia solium* infection even without laboratory confirmation. Similarly, in onchocerciasis-endemic villages of Cameroon, the contribution of infection with *O. volvulus* to epilepsy was very high (population-attributable fraction: 91.7%, 95% CI 56.7–98.4; p = 0.0021) [23]. Hence in communities with proven high ongoing transmission of *O. volvulus*, many epilepsies of "unknown" etiology could as well be caused by onchocerciasis.

### **3. Epilepsy management in specific settings**

About four fifth of PWE currently reside in LMICs where epilepsy care is often sub-optimal, resulting in a 75% treatment gap (proportion of PWE needing treatment who do not receive the necessary anti-epileptic drugs) [1]. It is therefore important to discuss epilepsy in these contexts, and propose ways to improve PWE management in such settings. Another special population worth looking into is the

women of reproductive age suffering from epilepsy. The risk with these women is the teratogenic effects of anti-epileptic drugs, which renders their management before, during, and after pregnancy quite delicate.

## **3.1 Managing epilepsy in resource-limited settings**

Improved management of PWE in resource-limited settings may be achieved by decentralizing epilepsy care. Approaches to diagnose and manage epilepsy and related complications can be simplified and taught to non-physicians, who will be in charge of running local epilepsy clinics under the supervision of physicians or specialists [27, 28]. Setting up a community-based epilepsy surveillance system will enable early diagnosis and treatment of PWE thereby preventing complications. To reduce the treatment gap, a regular supply of subsidized anti-epileptic drugs (AEDs) appropriate for different seizure types should be instituted. Daily intake of the adequate AEDs would eventually achieve seizure control in at least 70% of PWE [1]. The first-line AEDs that are routinely used in sub-Saharan Africa include phenobarbital, carbamazepine, phenytoin, and valproate [29]. Their indications and prescribed dosages as recommended by the WHO are detailed in **Table 1** [30]. AED treatment must be initiated as monotherapy with progressive dose increase based on the response to the treatment and seizure control. Phenobarbital, the most available and affordable AED (annual cost per PWE: 5 US dollars [29]), is used as first-line treatment for most seizure types but is not recommended for absences. It is usually initiated at 2–3 mg/kg/day and could be increased every 2–3 weeks by 15 mg if seizures continue, without going above the maximal recommended dose. When switching to another AED, phenobarbital should be tapered progressively (15 mg reduction every 2 weeks) while starting the newly prescribed AED as soon as the tapering begins. This approach minimizes the risk of rebound seizures upon stopping phenobarbital [31].

Besides the AEDs in **Table 1** which are commonly used in resource-limited settings, newer AEDs have been developed and are widely used in high-income countries; these include: gabapentin (GBP), topiramate (TPM), lamotrigine (LTG), levetiracetam (LEV), rufinamide (RFN), vigabatrin (VGB), oxcarbazepine (OXC), perampanel (PER), lacosamide (LCM) and eslicarbazepine acetate [36]. Although these are more expensive and less available in LMICs compared to the routine first-line AEDs, they are superior in achieving seizure control with relatively less side effects and fewer drug interactions.

Another essential component of epilepsy care in resource-limited settings is stigma reduction. In rural communities of Africa, PWE and their families are often stigmatized as a result of misconceptions regarding the origin and transmissibility of epilepsy [37]. Therefore, it is important that community awareness programs on epilepsy, as well as other interventions should be implemented to reduce stigma and facilitate the social rehabilitation of PWE [38].

### **3.2 Epilepsy in women of child-bearing age**

In addition to seizures and related complications experienced by all PWE, women with epilepsy (WWE) require a more comprehensive management strategy that takes into account reproductive health needs [39]. Indeed, optimal seizure control is recommended to ensure positive health and gestational outcomes for these women. However, most of the first-line AED routinely used in Africa (**Table 1**) may reduce the efficacy of hormonal contraceptives [40] or increase the risk for foetal malformations if taken during pregnancy [41]. Therefore, a tailored management approach is recommended for WWE and should include


**Table 1.** *Description of common first-line AEDs in resource-limited settings.* the following components: regular evaluation of the treatment regimen/dose and adjustments if needed; contraception and pre-conceptual counseling; psychosocial support and stigma-reducing interventions to improve their self-esteem and quality of life [42].
