EPILEPSY: A BRIEF REVIEW

 

{ DOWNLOAD AS PDF }

ABOUT AUTHORS
Abdul Waheed*, Swati Pathak, Roohi Mirza
Department of Pharmacology,
Amity Institute of Pharmacy,
Amity University, Noida, U.P., India
*abdul.waheed2050@gmail.com

ABSTRACT
Epilepsy is a chronic brain disorder characterized by tendency to recurrent seizures or fits. The seizures can leads to loss of consciousness, disturbance of movement, muscle spasms, autonomic and mental functions. Epilepsy is developed because of imbalance in nerve signalling chemical called neurotransmitters. During epilepsy, the level of excitatory neurotransmitter glutamate increases and the level of inhibitory neurotransmitter GABA decrease. These lead to abnormal signalling in brain causes epilepsy. Primary diagnosis of epilepsy includes eye–witness and family history. Electroencephalograph (EEG) is the cornerstone for diagnosis of epilepsy and measures the brain wave activity. Neuroimaging like computed tomography (CT) scan, magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques are used to diagnose abnormalities in structure and function of brain. Video recording is also useful for the monitoring of epileptic events. The most common approach of treatment is to prescribe antiepileptic drugs (AEDs). Three generations of AEDs including phenytoin, valproate, carbamazapine, lamotrigine, Oxcarbazepine, Primidone,Phenobarbitone,Gabapentin, Topiramate, Levetiracetam, Felbamate, Rufinamide, Zonisamide, Tiagabinand Vigabatrin etc. are prescribed. These AEDs have some teratogenic effects on  pragnent woman and lactating mother; need precautions. Instead of  pharmacological approaches, Non-pharmacological approaches also used for the treatment of epileptic seizures like ketogenic diet, atkins diet, yoga etc. Thr purpose of this review is to update the current knowledge on epilepsy classification, diagnostics, approaches of treatment, pathophysiology, mechanism of epileptogenesis and teratogenic effects.

REFERENCE ID: PHARMATUTOR-ART-2431

PharmaTutor (Print-ISSN: 2394 - 6679; e-ISSN: 2347 - 7881)

Volume 4, Issue 9

Received On: 10/01/2016; Accepted On: 12/04/2016; Published On: 01/09/2016

How to cite this article: Waheed A, Pathak S, Mirza R; Epilepsy: A brief review; PharmaTutor; 2016; 4(9); 21-28

OBJECTIVE
As per WHO epilepsy is one of the most common serious brain disorders that affects not only the individual, but also has impact on family and the society in general. Epilepsy affects all the ages, races, sex, education, economic status and social classes across all geographical boundaries. Hence need to aware about epilepsy.

INTRODUCTION
Epilepsy is a brain disorder that affects at least 12 millions people in India and 65 millions of people worldwide[1]. As per WHO epilepsy is one of the most common serious brain disorders that affects not only the individual, but also has impact on family and the society in general. Epilepsy affects all the ages, races, sex, education, economic status and social classes across all geographical boundaries.It is expressed by unpredictable recurrent seizures or fits, which can leads to loss of consciousness, disturbance of movement, muscle spasms, autonomic and mental functions. During the seizure, neurons may fire 500 times faster than normal neurons. Mechanism of epilepsy is believe to be imbalance in neurotransmitter release i.e. abnormally increase the level of excitatory neurotransmitter glutamate while decrease in inhibitory neurotransmitter GABA. Several types of epilepsy have now been linked to defective ion channels that control the flow of ions and regulate neuron signalling. Diagnosis includes eye–witness, family history, electroencephalograph (EEG), computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance spectroscopy (MRS) techniques. Most common approach to treating epilepsy is to prescribe antiepileptic drugs (AEDs). There are various older and newer AEDs like Gabapentin, Topiramate, Phenytoin, Valproate, Carbamazapine, Lamotrigine, Oxcarbazepine, Levetiracetam, Felbamate, Rufinamide, Zonisamide, Tiagabin, Vigabatrin, Primidoneand Phenobarbitone are used for the treatment of epilepsy. These drugs are use for symptomatic treatment of epilepsy that stops seizure but not cure the epilepsy. About 75—80% of epileptic patients respond to conventional antiepileptic drugs but in 20—25% cases therapeutic failures and refractoriness occur[2].In society there are many myths about epilepsy like (a) epilepsy is because of possession by evil sprit and hence sorcery is the treatment(b) epilepsy is mental illness (c) people with epilepsy are below normal in their intelligence (d) marriage cure epilepsy (e) seizure can be stopped by giving a key in the hand or making a person to smell onion or shoe. But this is not the fact; epilepsy is treated by giving antiepileptic drugs.

This work reviews the current knowledge on Classification,diagnostics, medications, Non-Pharmacological approaches, pathophysiology, mechanism of epileptogenesis and teratogenic effects.

PATHOPHYSIOLOGY OF EPILEPSY [3,4]
The first visible symptom of epilepsy is repeated seizure; generated due to malfunction of ion channels on synapses during neurotransmission. Primarily seizures are as result of hypoactivity of inhibitory neurotransmitter or hyperactivity of excitatory neurotransmitter. A persistent increase of neuronal hyperactivity or excitation is a single characteristic in most of the epileptic syndrome. The anomalous behaviour of neurons is associated with causative factors which are mainly categorized into two groups: Chemical Imbalance and Brain Injuries. Chemical imbalance includes low blood level of sodium, calcium, sugar and oxygen. Brain injuries include intercranial haemorrhage, brain oxygen deficiency, infection, trauma, tumour meningitis, stroke, and other neurological disorders. Other factors such as Genetic Factors and inflammation factors like Cytokines & tumour necrosis factor (TNF) are also involved. Neurological firing during seizure and pathophysiology of epilepsy are represented in fig 1. Role of neurotransmitter, ion channels and genetic factors in epilepsy are listed in table 1, 2 &3 respectively.

Figure 1:Neuronal firing during seizures. Neuronal firing is triggered by altered signal propagation. This may be the result of abnormalities in neuronal membrane stability or in the connections among neurons. Epileptic bursts consist of sodium dependent action potentials (1) and a calcium-dependent depolarizing potential (2). The opening of voltage activated Ca2+ channels and results in the flood of neurotransmitter (glutamate) into the synaptic cleft (3). Increased the accumulation of glutamate activate  N-methyl-D-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate receptors with consequent influx of Na+ and Ca2+ ions through the channels gated by these receptors leads to Neuronal hyper-excitability (4). Uncontrolled increase in Disinhibition is also one of the key events in the generation of epileptic seizures, since a reduction of GABAergic inhibition is necessary to produce the synchronous burst discharges in groups of cells (5).

Table 1: Role of neurotransmitters in epilepsy

Neurotransmitters

Role in epilepsy

GABA (γ amino butyric acid)

· Reduced GABA in microgyric cortex
· Reduced benzodiazepine receptor binding in medial thalamic nucleus (mesial temporal lobe epilepsy)
· Reduced benzodiazepine receptor density in CA1 region
· Reduced GABA levels and GAD activity (epileptic foci)
· Auto-antibodies to GAD (Stiff-man syndrome)

Glutamate

· Up regulation of hippocampal ionotropic glutamate receptors (temporal lobe epilepsy)
· Anti-gluR3 antibodies (Rasmussen encephalitis)
· Increased plasma glutamate levels (absence seizures)

Table 2: Role of Ions channels in epilepsy

Ions Channel

Role in epilepsy

Na+

Mutation voltage-gated Na+ channel (generalized epilepsy with febrile seizures)

K+

Mutation voltage-gated K+ channel
(benign familial neonatal convulsions)

Ca++

Reduced ACh-mediated Ca flux
(nocturnal frontal lobe epilepsy)

Table 3: Genetic factors of Epilepsies [5]

Epilepsy syndrome

Genetic cause

Generalized epilepsy with febril seizure type I &II

Type I: Point mutation in B1 subunit of a voltage gated sodium channel.

Type II: Point mutation in A1 subunit of a voltage gated sodium channel.

Benign Familial neonatal convulsions

Genes KCNQ2 & KCNQ3 at 20q & 8q chromosomes respectively of voltage gated potassium channel.

Autosomal dominant nocturnal frontal lobe epilepsy

Point mutation in the A4 subunit of neuronal nicotinic acetylcholine receptor on chromosomes 20q (CHRNA4) gene. This lead to reduce in GABA.

Episodic ataxia Type I

Point mutation on chromosome 12p13 of human voltage gated potassium channel gene.

Causes of Seizures and Epilepsy
Mechanisms of seizures are not clearly known but assumed to be a genetic factor that code for the Na+/ca++ ion channel protein; disturbance in inhibitory neurotransmitter GABA and excitatory amino acid Glutamate; brain injuries like stroke, infection, blow of head, high fever and tumor. Causes of seizures vary by age of person. One-third of children with autism spectrum disorder may have seizures. Seizures commonly begin in people over age of 60. Common causes of seizures are listed in table 4.

Table 4: Common causes of seizures by age[6]

Age

Causes

Newborn

· Brain malformations

· Lack of oxygen during birth

· Low levels of blood sugar, calcium, magnesium and other electrolytes

· Inborn errors of metabolism

· Intercranial haemorrhage

· Maternal drug use

Infants and Children

· Fever (febrile seizures)

· Brain tumour (rarely)

· Infections

Children and Adults

· Congenital conditions (Down's syndrome; Angelman's syndrome; tuberous sclerosis and neurofibromatosis)

· Genetic factors

· Progressive brain disease (rare)

· Head trauma

Classification of epilepsy:
Classificationof epilepsy is essential for understanding of epileptic seizure, correct diagnosis and first step towards correct treatment. It is helpful for both clinician and researcher. The International League Against Epilepsy (ILAE) published the last official update for the epilepsies in 1989. A report in 2010 by the ILAE Commission on Classification and Terminology recommended that changes be made in the current conceptualization, terminology, and definitions of seizures and epilepsy. Classification of epilepsy and syndromes are listed billow.

Classification of Epilepsy and syndromes [7]
1. Localisation-Related (Focal, Local, Partial)
Idiopathic
with age related onset
· Benign childhood epilepsy with centrotemporal spikes
· Childhood epilepsy with occipital paroxysms

Symptomatic
· Comprises syndromes of great individual variability, mainly based on:
· Anatomical localisation
· linical features
· Seizure types
· Etiological factors

(Epileptic syndromes of unknown etiology are classified as cryptogenic)

2. Generalised Epilepsies and Syndromes
Idiopathic
, with age related onset, listed in order of age
· Benign neonatal familial convulsions
· Benign neonatal convulsions
· Benign myoclonic epilepsy in infancy
· Childhood absence epilepsy (pyknolepsy)
· Juvenile myoclonic epilepsy
· Epilepsy with tonic-clonic seizures on awakening

Other generalised idiopathic epilepsies, if they do not belong to one of the above syndromes can still be classified as generalised idiopathic epilepsies

Idiopathic and/or symptomatic, in order of age of appearance
· West’s syndrome (infantile spasms)
· Lennox-Gastaut syndrome
· Epilepsy with myoclonic-astatic seizures
· Epilepsy with myoclonic absences

Symptomatic
Nonspecific etiology
· Early myclonic encephalopathy

Specific syndromes
· Epileptic seizures may complicate many disease states
· Included under this heading are those diseases in which seizures are a presenting or predominant feature

Epilepsies and Syndromes Undetermined as to Whether They Are Focal or Generalised
1. With both generalised and focal seizures
· Neonatal seizures
· Severe myoclonic epilepsy in infancy
· Epilepsy with continuous spike waves during slow wave sleep
· Acquired epileptic aphasia (Landau-Kleffner syndrome)

2. Without unequivocal generalised or focal features
· This heading covers all cases where clinical and EEG findings do not permit classification as clearly generalised or localisation-related, such as in many cases of sleep tonic-clonic seizures

Special Syndromes
1. Situation-related seizures
· Febrile convulsions
· Seizures related to other identifiable situations such as

  • Stress
  • Hormonal changes
  • Drugs
  • Alcohol
  • Sleep deprivation

2. Isolated, apparently unprovoked epileptic events
3. Epilepsies characterised by specific modes of seizure precipitation
4. Chronic progressive epilepsia partialis continua of childhood

NOW YOU CAN ALSO PUBLISH YOUR ARTICLE ONLINE.

SUBMIT YOUR ARTICLE/PROJECT AT editor-in-chief@pharmatutor.org

Subscribe to Pharmatutor Alerts by Email

FIND OUT MORE ARTICLES AT OUR DATABASE


Pages

FIND MORE ARTICLES