Dr H. Gharebaghian MD Neurologist

Department of Neurology

Kermanshah Faculty of Medicine

Definitions Seizures are transient events that include symptoms

and/or signs of abnormal excessive hypersynchronous activity in the brain

Epilepsy as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiological, cognitive, psychological, and social consequences of this condition

Definitions The traditional definition of epilepsy requires at least two

unprovoked seizures

The definition proposed by the ILAE in 2005 suggested that one epileptic seizure is sufficient to diagnose epilepsy if there is additional enduring alteration in the brain that increases the likelihood of future seizures

The proposed definition has been controversial and has not been widely accepted

Definitions Practical clinical definition:

Epilepsy was defined as a disease of the brain defined by any of the following conditions:

(1) At least two unprovoked seizures occurring >24 hours apart

(2) One unprovoked seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years

(3) Diagnosis of an epilepsy syndrome

Classification Needs for classification:

Variety of seizure types and epilepsies

Communication and diagnostic purposes

Evaluating drug specificity and prescribing the most appropriate therapy

Predict response to therapy and prognosis

Classification

ILAE diagnostic scheme for the classification of seizures and epilepsy recommend the following axes:

Axis 1: Ictal phenomenology

Axis 2: Seizure type

Axis 3: Syndrome (a syndrome diagnosis may not always be possible)

Axis 4: Etiology

Axis 5: Impairment

Classification Classifications developed by the ILAE continue to be used

widely:

Clinical and Electroencephalographic Classification of Epileptic Seizures published in 1981

Classification of Epilepsies and Epileptic Syndromes introduced in 1989

New ILAE classification for seizures and epileptic syndromes published in 2010

1981 classification of seizures

2010 classification of seizures New terminology and concepts that better reflect the current

understanding, while also striving for clarity and simplicity

Maintained the division of seizures based on generalized or focal onset but has recommended replacing “partial” with “focal”

Updated the definition of focal seizures as “originating within networks limited to one hemisphere,” with the possibility of the seizures being discretely localized or more widely distributed, and possibly originating in subcortical structures

Abandoned “simple”, “complex”, and “secondarily generalized”

2010 classification of seizures Generalized seizures were defined as “originating at some

point within, and rapidly engaging, bilaterally distributed networks,” which do not necessarily include the entire cortex

Revised concepts acknowledge that generalized seizures can be asymmetrical and that individual seizures may appear to have a localized onset, but the location and laterality of that onset will vary from seizure to seizure

2010 classification of seizures For focal seizures, the distinction between the different

types (e.g., complex partial and simple partial) is eliminated

It is important, however, to recognize that impairment of consciousness/awareness or other dyscognitive features, localization, and progression of ictal events can be of primary importance in the evaluation of individual

2010 classification of seizures Descriptors of focal seizures according to degree of

impairment during seizure:

Without impairment of consciousness or awareness

With impairment of consciousness or awareness (Dyscognitive). This roughly corresponds to the concept of complex partial seizure

Evolving to a bilateral, convulsive seizure (involving tonic, clonic, or tonic and clonic components). This expression replaces the term ‘‘secondarily generalized seizure.’’

2010 classification of seizures

1989 classification of epilepsies

2010 classification of epilepsies Abandoned Localization-related vs generalized.

Syndromes were arranged by age at onset.

Instead of the terms idiopathic, symptomatic, and cryptogenic, the following three terms were recommended:

1. Genetic- the epilepsy is the direct result of a known or presumed genetic defect in which seizures are the core symptom of the disorder

2. ‘‘Structural/metabolic’’

3. ‘‘Unknown cause’’

2010 classification of epilepsies ‘‘syndrome’’ will be restricted to a group of clinical

entities that are reliably identified by a cluster of electroclinical characteristics

Patients whose epilepsy does not fit the criteria for a specific electroclinical syndrome can be described with respect to a variety of clinically relevant factors (e.g., known etiology and seizure types)

This does not, however, provide a precise (syndromic) diagnosis of their epilepsy

2010 classification of epilepsies A number of entities that are not exactly electroclinical syndromes

but which represent clinically distinctive constellations on the basis of specific lesions or other causes.

These are diagnostically meaningful forms of epilepsy and may have implications for clinical treatment, particularly surgery.

These include mesial temporal lobe epilepsy (with hippocampal sclerosis), hypothalamic hamartoma with gelastic seizures, epilepsy with hemiconvulsion and hemiplegia, and Rasmussen ‘‘syndrome.’’

Age at presentation is not a defining feature in these disorders, as we understand them; however, they are sufficiently distinctive to be recognized as relatively specific diagnostic entities

2010 classification of epilepsies

2010 classification of epilepsies

Major symptomatic epilepsies

Genetic/congenital epilepsies

Acquired epilepsies

Brain malformations In children, developmental brain malformations are an

important cause of epilepsy

These can be generalized, hemispheric, or focal

They are also classified as related to:

Abnormal cell proliferation or differentiation including tuberous sclerosis, focal cortical dysplasia, and hemimegalencephaly

Abnormal neuronal migration, including lissencephaly, subcortical band heterotopias, and periventricular nodular heterotopias

Abnormal cortical organization, including polymicrogyria and schizencephaly

Brain malformations Some of these malformations are genetically determined

Many of these malformations have other associated neurological disorders or physical findings

Focal malformations associated with epilepsy are less likely to have other neurological manifestations than hemispheric or generalized malformations

The severity of epilepsy and its response to therapy can be quite variable, but it is commonly drug-resistant, prompting evaluation for surgical treatment

Brain malformations

Scizencephaly Lissencephaly Tuberous sclerosis

Head trauma Head trauma is an important risk factor for epilepsy, with the

greatest risk seen in association with penetrating head injury, depressed skull fracture, and severe head trauma

Mild traumatic brain injury (characterized by absence of fracture and a loss of consciousness or post-traumatic amnesia for less than 30 min) is associated with only a 1.5-fold increase in risk

Moderate head injury (defined as loss of consciousness or post-traumatic amnesia for 30 minutes to 24 hours or a skull fracture), is associated with a 2.9-fold increase in risk

Severe head injury (including brain contusion or intracranial hematoma or loss of consciousness or post-traumatic amnesia for more than 24 hours), is associated with 17-fold increased risk

Head trauma The risk was highest in the first year after the injury but

remained increased thereafter for a duration that varied with severity of the injury

For those with moderate brain injuries, the risk was markedly increased for up to 10 years only; for those with severe traumatic brain injury, the risk continued to be increased

Early seizures appeared to be a strong risk factor for late seizures, but early seizures were usually related to the severity of the head injury and intracranial lesions

Phenytoin and Levetiracetam are effective in preventing seizures in the first week

Vascular Malformations The two vascular malformations most commonly associated with

epilepsy are arteriovenous malformations and cavernous malformations

Arteriovenous malformations (AVMs) are high-pressure vascular malformations with arteriovenous shunting. They are a tangle of feeding arteries and draining veins without intervening capillary bed

They may come to attention during evaluation for seizures or after they bleed; or may be incidental finding on imaging

Because of the high pressure, they are susceptible to bleed at a rate of 1% to 3% per year, which is the main reason they require therapy

Treatment options include: Surgical resection, Endovascular treatment with embolization and radiosurgery

Vascular Malformations Cavernous malformations consist of blood-filled epithelium lined

caverns with no discrete arteries or veins On MRI they have a characteristic “popcorn” appearance with mixed

signal within the lesion and a rim of decreased signal, reflecting hemosiderin

They may be multiple in approximately a third of cases Cavernous malformations are low-pressure lesions with a much

smaller risk of bleeding than AVMs They are strongly associated with epilepsy If seizures are controlled with medical therapy, there is no clear

indication for surgical resection when epilepsy is drug resistant, resection of the cavernous

malformation is associated with excellent results

Vascular Malformations

Cavernous malformation Arteriovenous malformation

Brain Tumors Brain tumors are a common cause of epilepsy, particularly drug-

resistant epilepsy. Most drug-resistant epilepsy occurs with low-grade tumors,

especially those in the temporal lobe Benign tumors associated with epilepsy are gangliogliomas,

dysembryoblastic neuroepithelial tumors (DNET), and low grade gliomas

Excellent seizure control most often occurs after removal of gangliogliomas and DNET tumors

Seizures contribute to the morbidity of malignant brain tumors in approximately a quarter of patients

Grade 3 anaplastic astrocytomas are more likely to present with seizures at onset than glioblastoma multiforme

Brain Tumors

GBM Meinigioma Metastasis

Stroke Stroke increases the risk of seizures and epilepsy at any

age

It is the most common cause of seizures in the elderly

Early seizures that occur within 2 weeks of the stroke

The risk of chronic epilepsy is highest in the first year after stroke, with a 17-fold increase in the risk

Compared to individuals who did not have early seizures, approximately 30% of individuals who have early post-stroke seizures develop later epilepsy. This is a 16-fold increase in risk

Stroke Seizures and even status epilepticus can be a presenting

symptom of acute stroke.

Strokes involving the cortex are more likely to produce epilepsy than deep white-matter strokes

The incidence of seizures is also higher in patients with intracerebral hemorrhage

Prophylactic AED therapy is contraversial

Autoimmune Disorders Immune disorders increase the risk of epilepsy and seizures

In SLE, the risk of seizures is 12% to 20% and is more likely with anticardiolipin and anti-Sm antibodies

Between 2% and 6% of patients with multiple sclerosis have seizures. Those who do tend to have more extensive cortical involvement. Seizures are more likely to occur in the context of acute relapse, but some patients develop chronic epilepsy

Seizures are a more common acute manifestation of acute disseminated encephalomyelitis, (approximately 50%). However, chronic epilepsy is much less likely (only about 5% )

Autoimmune Disorders Limbic encephalitis is an increasingly recognized cause of

epilepsy

Suggested diagnostic criteria include one of disturbance of episodic memory, temporal lobe seizures, or affective disturbance plus the presence of either well-characterized antibodies or unexplained increased signal in the mesial temporal structures, or histopathology of mesial temporal encephalitis

It can be paraneoplastic or nonparaneoplastic

Paraneoplstic cases are associated with small cell lung cancer, testicular cancer, thymoma, breast cancer, or teratoma

Autoimmune Disorders An immune basis of epilepsy should be suspected in

individuals who have other autoimmune disease, abrupt or recent onset of seizures (particularly if resistant to AEDs and progressive in frequency and severity), associated manifestations such as behavioral changes and psychosis, severe memory disturbances, and abnormal signal on MRI in the hippocampi

An immune origin is suspected in several well-described epileptic syndromes. These include West syndrome, Lennox-Gastaut syndrome, LKS, and Rasmussen syndrome

Acute Symptomatic Seizures Acute symptomatic seizures occur in close temporal

relationship with an acute CNS insult—metabolic, toxic, structural, infectious, or inflammatory

Metabolic disturbances known to cause seizures include hypoglycemia, hyperglycemia, hyponatremia, hypocalcemia, hypomagnesemia, and uremia

Withdrawal from chronic alcohol abuse, benzodiazepines and barbiturates (more commonly with short acting agents) may be associated with generalized tonic-clonic seizures

Acute Symptomatic Seizures Several illicit drugs produce acute symptomatic seizures,

particularly cocaine and other stimulants

Several therapeutic medications can trigger acute symptomatic seizures at high doses or in susceptible individuals

These same medications, as well as metabolic derangements, can also trigger seizures in people with epilepsy, at lower thresholds than for people without epilepsy

Metabolic and toxic causes of acute symptomatic seizures do not usually cause chronic epilepsy

Provoked epilepsy The category of provoked epilepsy is differentiated from both

idiopathic and symptomatic epilepsy

Provoked epilepsy is defined as: An epilepsy in which a systemic or environmental factor is the predominant cause of the seizures and in which there are neuropathological or neuroanatomical changes

Many patients with provoked seizures have an increased susceptibility to epilepsy (either genetic or acquired) and the term provoked epilepsy should be applied where the overwhelming influence is the provoking factor and not the underlying susceptibility

Provokative factors: Fever; menstrual cycle and catamenial epilepsy; sleep; startle

Self assessment questions

The diagnosis of epilepsy can be made after : A.Two unprovoked seizures >24 hours apart

B.Two unprovoked seizures <24 hours apart

C.One unprovoked seizure if there is a coexisting brain lesion

D.One provoked seizure and a second unprovoked seizure

Thank you

References 1. Neurology in clinical practice, Bradley 2016

2. New concepts in classification of the epilepsies: Entering the 21st century

3. Seizures and Epilepsy: Pathophysiology and Principles of Diagnosis

4. The causes of epilepsy

5. Harrison 2015