All about Epilepsy- Dr Srikant Sharma

National Epilepsy Day in India is celebrated on 17th November by the Epilepsy Foundation with an aim to raise awareness about epilepsy among people living in India. Dr Srikant Sharma has very vividly covered all aspects of Epilepsy to mark this occasion.

A seizure (from the Latin sacire, “to take possession of”) is a transient occurrence of signs or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Epilepsy describes a condition in which a person has a risk of recurrent seizures due to a chronic, underlying process. It refers to a clinical phenomenon rather than a single disease entity because there are many forms and causes of epilepsy.

CLASSIFICATION OF SEIZURE-
1. Focal seizures
2. Generalized onset – motor or non-motor
3. Seizure of unknown onset

Focal seizure with intact awareness- Focal seizures can have motor manifestations or nonmotor manifestations without impairment of awareness. The additional features of focal motor seizures –1. Jacksonian march- represents the spread of seizure activity over a progressively larger region of motor cortex. 2. Todd’s paralysis- localized paresis for minutes to many hours in the involved region following the seizure. 3. Epilepsia partialis continua- the seizure may continue for hours or days is often refractory to medical therapy. Focal seizures arising from the temporal or frontal cortex may also cause alterations in hearing, olfaction, or emotional state. This includes the sensation of unusual, intense odours (e.g., burning rubber or kerosene) or sounds (crude or highly complex sounds), or an epigastric sensation that rises from the stomach or chest to the head.

Focal Seizures with Impaired Awareness - transient impairment of the patient’s ability to maintain normal contact with the environment and patient is unable to respond appropriately to visual or verbal commands during the seizure and has impaired recollection or awareness of the ictal phase. Aura followed by impaired awareness with automatism (chewing, lip-smacking, swallowing, or “picking” movements of the hands) followed by confusion and then full recovery. Examination immediately following the seizure may show anterograde amnesia or transient neurological deficits (such as aphasia, hemineglect, or visual loss) caused by postictal inhibition of the cortical regions most involved in the seizure itself.

• Typical Absence Seizures- sudden, brief lapses of consciousness without loss of postural control which usually lasts for only seconds, consciousness returns as suddenly as it was lost, and there is no postictal confusion. EEG shows generalized, symmetric, 3-Hz spike-and-slow-wave discharges that begins and ends suddenly, superimposed on a normal EEG background.


• Atypical Absence Seizures- features that deviate both clinically and electrophysiologically from typical absence seizures. The EEG shows a generalized, slow spike-and-slow-wave pattern with a frequency of ≤2.5 per second, as well as other abnormal activity.


• GENERALISED TONIC CLONIC SEIZURES- premonitory symptoms / prodrome followed by usually tonic contraction of muscles throughout the body (ICTAL CRY- muscles of larynx and expiration), marked enhancement of sympathetic tone leads to increases in heart rate, blood pressure, and pupillary size following which clonic phase, produced by the superimposition of periods of muscle relaxation on the tonic muscle contraction. Then there is a postictal phase
  which has unresponsiveness, muscular flaccidity, and excessive salivation that can cause stridulous breathing and partial airway obstruction, Bladder or bowel incontinence followed by postictal confusion. EEG in tonic phase of the seizure - shows a progressive increase in generalized low-voltage fast activity, followed by generalized high-amplitude, polyspike discharges. In the clonic phase- the high-amplitude activity is typically interrupted by slow waves to
  create a spike-and-slow-wave pattern. In postictal phase- diffuse suppression of all cerebral activity, then slowing that gradually recovers as the patient awakens.


• Atonic seizures- sudden loss of postural muscle tone lasting 1–2 s. Consciousness is briefly impaired, but there is usually no postictal confusion. A very brief seizure may cause only a quick head drop or nodding movement, whereas a longer seizure will cause the patient to collapse. EEG shows brief, generalized spike-and-wave discharges followed immediately by diffuse slow waves that correlate with the loss of muscle tone.


• Myoclonic seizures- Myoclonus is a sudden and brief muscle contraction that may involve one part of the body or the entire body. A normal, common physiologic form of myoclonus is the sudden jerking movement observed while falling asleep. Pathologic myoclonus is most commonly seen in association with metabolic disorders, degenerative CNS diseases, or anoxic brain injury.

Causes as per age:

Age group	Causes
Neonates (<1 month)	Perinatal hypoxia and ischemia Intracranial haemorrhage and trauma CNS infection Metabolic disturbances (hypoglycemia, hypocalcemia, hypomagnesemia, pyridoxine deficiency) Genetic disorders
Infants and children (>1 month and <12 years)	Febrile seizures Genetic disorders (metabolic, degenerative, primary epilepsy syndromes) CNS infection Developmental disorders Trauma
Adolescents (12–18 years)	Trauma Genetic disorders Infection Illicit drug use Brain tumour
Young adults (18–35 years)	Trauma Alcohol withdrawal Illicit drug use Brain tumour
Older adults (>35 years)	Cerebrovascular disease Brain tumour Alcohol withdrawal Metabolic disorders (uremia, hepatic failure, electrolyte abnormalities, hypoglycemia, hyperglycemia) Alzheimer’s disease and other degenerative CNS Diseases

APPROACH TO PATIENT :

• History and examination


• Risk factors


• Precipitating factors


• Neurological examination


• Signs of head trauma and the use of alcohol or illicit drugs should be sought.

Lab studies-

• Routine blood studies are indicated to identify the more common metabolic causes of seizures such as-


• abnormalities in electrolytes, glucose, calcium, or magnesium, and hepatic or renal disease.


• Toxic screen


• lumbar puncture is indicated if there is any suspicion of meningitis or encephalitis, and it is mandatory in all patients infected with HIV, even in the absence of symptoms or signs suggesting infection.

EEG- All patients who have a possible seizure disorder should be evaluated with an EEG as soon as possible.

• The absence of electrographic seizure activity does not exclude a seizure disorder, however, because focal seizures may originate from a region of the cortex that cannot be detected by standard scalp electrodes.


• The EEG is always abnormal during generalized tonic-clonic seizures.


• Because seizures are typically infrequent and unpredictable, it is often not possible to obtain the EEG during a clinical event.


• Activating procedures commonly include hyperventilation (for 3 or 4 min), photic stimulation, sleep, and sleep deprivation on the night prior to the recording.

IMAGING- MRI - indications are epilepsy starting after the age of 16 years, Seizures having focal features clinically, EEG showing a focal seizure source, control of seizures difficult or deteriorating.

Structural causes of epilepsy that can be identified by MRI include-

• Mesial temporal sclerosis (hippocampal sclerosis)


• Malformations of cortical development (eg, cortical dysplasia)


• Brain tumours


• Vascular malformations


• Cerebral infarction, cerebral haemorrhage


• Traumatic brain injury


• Infections, including encephalitis, cerebral abscess, granulomas, and cysts (neurocysticercosis)


• Functional imaging procedures such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are also used to evaluate certain patients with medically refractory seizures

SPECT- a radiolabeled tracer (eg, 99mTc-hexamethyl-propylene amine oxime [99mTc- HMPAO]) is injected and binds on first pass through the brain. Thus, a SPECT study provides a snapshot of cerebral circulation at the time of injection. The tracer is stable for several hours, allowing delayed imaging of blood flow at the time of injection.

In patients with focal epilepsy,

• Ictal SPECT studies - show hyperperfusion at the seizure focus with surrounding hypoperfusion.SPECT can be useful in the identification of a possible epileptic focus, particularly when MRI is unremarkable, to identify a potential localization for the seizure focus that can be further tested with intracranial electroencephalography (EEG) studies

TREATMENT OF EPILEPSY- It is Multimodal and mainly the treatment of underlying conditions that cause or contribute to the seizures. Also avoidance of precipitating factors and Suppression of recurrent seizures by prophylactic therapy with antiepileptic medications or surgery, and addressing a variety of psychological and social issues.

ANTIEPILEPTIC DRUG THERAPY- it is the mainstay of treatment for most patients with epilepsy. To completely prevent seizures without causing any untoward side effects, with a single medication and with an easy dosing schedule. Seizure classification is an important element in designing the treatment plan. However, the choice of therapy is often determined more by the patient’s specific needs & side effects.

When to Initiate Antiepileptic Drug Therapy??

• Recurrent seizures of unknown etiology


• single seizure with epileptogenic foci.


• Presence of 1 or more risk factors associated with recurrent seizures include the following:

(1) an abnormal neurologic examination,
(2) seizures presenting as status epilepticus,
(3) postictal Todd’s paralysis,
(4) a strong family history of seizures (SLC2A1, ALDH7A1),
(5) an abnormal EEG.

Focal Seizures Treatment - Carbamazepine (or a related drug, oxcarbazepine), lamotrigine, phenytoin, and levetiracetam are currently the drugs of choice. Similar efficacy, but differences in pharmacokinetics and toxicity are the main determinants for use in a given patient. Lamotrigine tends to be well tolerated in terms of side effects. It leads to Stevens-Johnson syndrome if unrecognized and if the medication is not discontinued immediately. This risk can be reduced by the use of low initial doses and slow titration.

Phenytoin shows properties of nonlinear kinetics causing acute phenytoin toxicity. Long-term use of phenytoin is associated with untoward cosmetic effects. Due to these side effects, phenytoin is often avoided in young patients who are likely to require the drug for many years.

Levetiracetam has no known drug-drug interactions, making it especially useful in the elderly and patients on other medications.

Valproic acid is an effective alternative for some patients with focal seizures, especially when the seizures generalize. Gastrointestinal side effects are fewer when using the delayed-release formulation (Depakote). Laboratory testing is required to monitor toxicity because valproic acid can rarely cause reversible bone marrow suppression and hepatotoxicity, hyperandrogenism, neural tube defects, Irreversible, fatal hepatic failure in children <2 years old

Generalized Seizures -levetiracetam, Lamotrigine, and valproic acid are currently considered the best initial choice.

Topiramate, zonisamide, phenytoin, carbamazepine, and oxcarbazepine are suitable alternatives.

Valproic acid commonly used in patients with generalized epilepsy syndromes having mixed seizure types.

Absence seizure-Ethosuximide is a particularly effective drug for the treatment of uncomplicated absence seizures. Lamotrigine is also an alternative to valproate, especially for absence epilepsies. Monitoring the dose of the antiepileptic drug-

• for documenting adherence or assessing clinical suspicion of toxicity


• The key determinants are seizure frequency and the presence of side effects, not the laboratory values.


• it is the concentration of free drug that reflects extracellular levels in the brain and correlates best with efficacy.


• Thus, patients with decreased levels of serum proteins due to the impaired liver or renal function have “subtherapeutic” drug level due to high serum-free to bound drug.

WHEN TO DISCONTINUE THERAPY?

After 2 years, all of the following criteria :

(1) complete medical control for 1–5 years
(2) single seizure type, with generalized seizures
(3) normal neurologic examination, including intelligence
(4) no family history of epilepsy
(5) normal EEG

it is preferable to reduce the dose of the drug gradually over 2–3 months. Most recurrences in the first 3 months after discontinuing therapy, so advised to avoid driving or swimming. So most states allow patients to drive after a seizure-free interval (on or off medications) of between 3 months and 2 years.

CONTRACEPTION

• carbamazepine, phenytoin, phenobarbital, Lamotrigine and topiramate decrease the efficacy of oral contraceptives via enzyme induction.


• So other methods of contraception should be used.


• Sodium valproate and levetiracetam have no interaction with hormonal contraception.

IN BREASTFEEDING MOTHERS

• Given the overall benefits of breastfeeding and the lack of evidence for long-term harm to the infant by being exposed to antiepileptic drugs, mothers with epilepsy can be encouraged to breast-feed.


• should be reconsidered, if drug effects seen on the infant (lethargy or poor feeding).

IN PREGNANCY: Levetiracetam may be safe.

When to get alert in epilepsy: seizure lasts longer than 5 minutes. Repeated seizures. Seizures underwater. Seizures with breathing difficulty. A person is injured pregnant or sick. After seizures, if not return to the usual conscious state.

Some patients with drug-resistant epilepsy may need vagal nerve stimulation for deep brain stimulation. All those who continue to experience seizures despite appropriate above therapies should be considered for surgical treatment.

Dr Srikant Sharma, Senior Consultant, Moolchand Hospital, New Delhi And Dr Aayushi Gupta, DNB resident, Moolchand Hospital, New Delhi.