Epidemiology, Aetiology and Diagnosis of Epilepsy

Question 1

What is epilepsy?

Answer 1

Epilepsy is not just one condition, but a group of many different ‘epilepsies’ with one thing in common: a tendency to have seizures that start in the brain.

Question 2

What are the three ways epilepsy can be defined/diagnosed?

Answer 2

Following two unprovoked seizures more than 24 hours apart or
Following one unprovoked seizure and a probability of further seizures similar to that of having two unprovoked seizures (60% over 10 years) or
Diagnosed with epilepsy syndrome

Question 3

Define the characteristic symptom of epilepsy.

Answer 3

Epilepsy is categorised by the presence of seizures which is transient occurrence of signs or symptoms due to abnormal, excessive or synchronous neuronal activity in the brain

Question 4

What is the prevalence of epilepsy?

Answer 4

70 million worldwide which equates to roughly 5-10 cases per 1000 however this is not equal geographically and is difficult to give an accurate statistic as diagnosis is difficult

Question 5

Where in the world has the highest incidence of epilepsy?

Answer 5

Roughly 80% diagnosed with epilepsy live in low-middle income countries.

Question 6

Why is it believed that incidence of epilepsy is higher in poor-middle income countries?

Answer 6

Perhaps due to prevalence of endemic conditions such as incidence of malaria (cerebral malaria in particular is linked to development of epilepsies) in addition to road traffic accidents and birth defects which may also be a cause.

Question 7

What percentage of patients with epilepsy are not receiving adequate treatment?

Answer 7

75%

Question 8

Is there any demographic characteristics that increase epilepsy incidence?

Answer 8

No epilepsy affects both genders, races and ages however the incidence is highest in infants, over 50s and those with learning disabilities.

Question 9

Does epilepsy have a reduced life expectancy?

Answer 9

Although most patients with epilepsy do not die directly from the condition itself, there is a reduced life expectancy of on average 12 years for men and 11 years for women with epilepsy.
However there is a lower risk in newly diagnosed, controlled epileptics.

Question 10

What are some of the conditions or contributing factors for pre-mature death in epilepsy?

Answer 10

Seizure related accidental injuries
Status epilepticus
Side effects/ADRs from AEDs
Suicide
SUDEP

Alongside co-morbidities for instance or unrelated such as cancer.

Question 11

State the five underlying aetiologies of epilepsy.

Answer 11

Structural
Genetic
Infection
Metabolic
Immune

Question 12

Explain the structural aetiology of epilepsy.

Answer 12

Structural abnormalities that have caused epilepsy (also known as structural epilepsy) can be categorised into:
Congenital- cerebral malformations which may have underlying genetic causes. May present as early as in infants or as late as early adulthood.
Acquired- malformations due to an inherent change or injury to a previous normal brain structure. This includes following a stroke, brain tumour or after head trauma.

Question 13

Are there any recognised genetic mutations which have been linked to increased prevalence of epilepsy?

Answer 13

It appears there is a lot of clinical research underway to identify genetic mutations attributed to epilepsy development, it appears genetic mutations associated with epilepsy can be subdivided into:

Epilepsy genes (genes that only cause epilepsies or syndromes with epilepsy as the core symptom).

Neurodevelopment-associated genes (genes associated with gross brain developmental malformations and epilepsies).

Epilepsy-related genes (genes associated with gross physical, or other systemic abnormalities and accompanied by epilepsy or seizures).

It is estimated that more than half of epilepsies have a genetic basis, however these do not always have to be inherited.

Question 14

What is the genetic mutations associated with the onset of Dravet’s syndrome?

Answer 14

SCN1A which makes up NaV 1.1 propagating neuronal signalling.
90% of SCN1A mutations are de novo, meaning they are not found in the patient’s parents and most commonly there are missense, nonsense or frameshift mutations.

Question 15

Which infections are associated with incidence of epilepsy?

Answer 15

Usually infections within the brain such as:
Cerebral malaria (linked to high incidence in low and middle income countries).
CNS Tuberculosis (20% go on to develop seizures)
Bacterial acute meningitis
Cerebral abscesses

However this is not extensive and can also occur as a result of fungal or viral infection (Human herpes virus-6) also.

Question 16

Explain the metabolic aetiology of epilepsy.

Answer 16

Metabolic disorders can cause seizures through one of three ways: deficiency of substrates essential for cellular metabolism or membrane function, intracellular accumulation of toxic substances and alteration of intracellular osmolality.

Question 17

What are some of the metabolic conditions that can cause seizures/epilepsy?

Answer 17

Metabolic conditions that can cause epilepsy include GLUT-1 deficiency essential starving the brain and causing seizures; Creatine disorders; Biotinidase deficiency.

Question 18

Explain the immune mediated aetiology of epilepsy.

Answer 18

This occurs when there is auto-immune mediated central nervous system inflammation, where the core symptom of the condition are seizures.

Question 19

What is anti-NMDA encephalitis?

Answer 19

Anti-NMDA (N-methyl-D-aspartate) receptor encephalitis is autoimmune disorder, in which antibodies are directed against the NMDA receptor in the brain, resulting in neurologic and psychiatric symptoms.

NMDA receptors play a critical role in normal brain function. NMDA receptors are present throughout the brain and are a key receptor in signaling from neuron to neuron. Therefore, when they are prevented from working normally by an antibody, multiple areas of the brain are affected. This is why you can have very different symptoms affecting different parts of the brain (seizures, movement disorder, psychosis, memory loss).

Anti-NMDAR encephalitis is the most common form of antibody-associated autoimmune encephalitis and affects women more commonly at a 8:2 ratio.

Question 20

What is the importance of identifying the cause of epilepsy or seizure onset?

Answer 20

The epilepsy can be managed a lot of effectively by also potentially treating the underlying cause (for example management of a brain tumour).

Question 21

List the risk factors for epilepsy.

Answer 21

Premature birth
Family history of epilepsy or neurological disease
Complicated febrile seizures
Brain development malformations
Head trauma
Tumours
Infection (meningitis or encephalitis)
Cerebrovascular disease/Stroke
Dementia/Neurological disorders
Drugs/Alcohol withdrawal

Question 22

What is the first stage of getting an epilepsy diagnosis?

Answer 22

After the onset of the first seizure, patient should be referred urgently (within 2 weeks) including afebrile in children to a specialist in which an eyewitness account should be provided or a video recording of their seizure to provide a complete history of the seizure.

Assess the patients risk of having a second seizure.

Question 23

What are some of the modifiable risk factors in adults that may increase their risk of a second seizure occurring?

Answer 23

-Underlying mental health problem (such as depression, anxiety, psychosis and alcohol or substance misuse)

-Vascular risk factors (for example, diabetes, hypertension, atrial fibrillation)

-Sepsis

Question 24

What advice should be provided to the patient, family and friends following a seizure?

Answer 24

-How to recognise a further seizure
-First aid and initial safety guidance in case of another seizure
-Any changes they can make to reduce their risk of another seizure
-Who they should contact if they have a further seizure while awaiting their appointment for assessment and diagnosis

Question 25

What are some of the investigations that can be made for epilepsy?

Answer 25

-Electroencephalogram only to support not exclude diagnosis normally a routine, but sometimes can be a sleep-deprived one
-Full blood count - detect infectious causes
-Antibody testing if auto-immune encephalitis is suspected in new onset epilepsy
-Genetic testing
-U&Es
-ECG (12-lead ECG to help identify cardiac-related conditions that could mimic an epileptic seizure)
-Neuropsychological assessment to evaluate cognitive function in relation to language and memory
-Neuroimaging (MRI/CT for structural abnormalities)

Question 26

Are all of the above investigations always made in an epileptic diagnosis?

Answer 26

No it depends on the symptoms linked to seizure type and appropriateness of the investigations.