EPILEPSY

Demographics

Most common serious neurological condition

Incidence 50-70 cases per year (of a" causes except febrile seizures)

Greatest in young chidren and elderly

Prevalenc 5-10 per 1000

Lifetime prevalence 2-5% of the population

Slightly more common in males than females

Slightly more common in lower social classes

Frequency of seizure activity in population:

33% less than one seizure per year

33% 1-12 seizures per year

33% more than 1 seizure per month

60% with active epilepsy also have neuropsychiatric problems:

·learning difficulty

·behavioural disturbance

·discrete cognitive impairment focal neurological deficit

Classification of Seizures

Primary Generalised

Widespread involvement of both hemispheres simultaneously - exact mechanism unknown

Clinical Manifestations:

Grand Mal: · sudden loss of consciousness

tonic phase (EEG- 8-l2/sec high amplitude spikes)

clonic phase(EEG -above interrupted by slow waves)

sleep or disorientation(EEG-low amplitude delta)

Petit Mal: . absence attacks - altered consciousness

· atonic seizure - loss of muscle tone

(EEG - 3 c/s spike and wave complexes)

Partial Epilepsies

Focal activity giving rise to symptoms reflecting function of area involved

if activity 'progresses' to involve motor areas get a secondary generalised seizure

Simple Partial:

·no loss of consciousness

·motor or sensory disturbance

·lesion in primary cortex

Complex Partial:

altered consciousness

·disturbance of higher mental function

,lesion in association cortex or limbic system

Occurence of seizures types in population

40% primary generalised tonic-clonic seizures

20% secondary generalised tonic-clonic seizures

20% complex partial seizures

12% mixed tonic-clonic and partial seizures

3% simple partial seizures

5% absence and other types

Epileptic Auras

Early ictal phenomena from the epileptic focus before any progression.

Frontal -motor symptoms such as discrete movements or speech arrest

TL-like symptoms

Parietal -sensory symptoms

-disorders of body image

occipital -visual disturbances such as scotomata, simple visual hallucinations

Temporal -autonomic symptoms e.g. epigastric, salivation, flushing, vertigo

Limbic -psychosensory e.g. illusions, hallucinations, depersonalisation, deja vu

-cognitive e.g. disturbance of speech, thought and memory

-affective e.g. fear and anxiety, depression, pleasure (rare)

Psychomotor Epilepsy

Complex behaviours representing ongoing epileptic discharge Not necessarily a temporal lobe focus

Automatisms -duration of minutes

-ictal or post-ictal

-impaired consciousness

-simple or complex movements

-amnesia

Fugue -duration of hours or days

-? post-ictal

-impaired consciousness

-abnormal complexbehaviour

-amnesia

Twighlight States -hours in duration

-ictal or post-ictal

-impaired consiousness

-cognitive and affective changes

-delusions and hallucinations

-partia1 recall

Petit Mal Status -minutes to hours in duration

-ictal

-speech perseveration

-incoordination

-psychomotor slowing

-terminated by environmental stimuli

-amnesia

Aetiology of Epilepsy

Clinico-Pathological Basis of Epilepsy

cryptogenic: minor congenital anomolies primary epilepsy

genetic basis (neuronal developmental defects)

15% cerebrovascular disease

6% alcohol related

3% post-traumatic secondary epilepsies

3% post-infective

others: neurodevelopmental disorders, neurodegenerative disease, tumours, metabolic etc

Cellular and Molecular and Basis of Epilepsv

Epilepsy = excessively synchronous discharge of an aggregate of neurones

Hypothetical causes:

A. Disorder of neuronal migration Genetic or intrauterine infection (e.g CMV):

e.g. TLE - associated with heterotopia - clusters of neurones subcortical white )

e g. Primary generalised epilepsy associated wit microdysgenesis- abnormal neurones

B. Mesial temporal sclerosis:

Selective loss of pyramidal neurones in CAl, CA3 and CA4 subfields of hippocampus

Common fmding at post mortem of institutionalised epileptics

Common fmding in anterior temporal lobectomy specimens

Caused by uncurbed seizure activity during brain development

(>50% surgical patients have history of prolonged febrile convulsions in infancy)

Cell loss causes secondary regenerative changes promoting focal epileptogenesis later in life

(e.g. excessive neuronal sprouting alters excitatory/inhibitory neuronal balance)

C.Decreased GABAereic Inhibitorv Neurotransmission:

GABA is the major inhibitory neurotransmitter system in the brain

- long tracts

- interneurones

In hippocampus and cortex, recurrent GABA interneurones prevent excessively sustained discharge or from principle neurones

Drugs blocking GABA transmission are epileptogenic

Benzodiazepines bind to a site on GAB AA receptor and promote action of GABA

Pyridoxine dependent convulsions in man - genetic deficiency of GABA synthesis

Alumina applied to monkey cortex - specific loss of GABA neurones and seizures

D.Increased Glutamate Excitatory Neurotransmission:

Glutamate is an excitatory neurotransmitter with several receptor types e.g. NMDA, kainate

NMDA receptor antagonists are anticonvulsants in animal models

Increased kainate and NMDA receptors in hippocampi of temporoal lobectomy specimens

Enhanced sensitivity of NMDA receptors in humans with ThE

E.Membrane Conductance Abnormalities:

Calcium conductance contributes to rhythmic firing in thalamus

Probably involved in 3c/s spike and wave activity

Calcium conductance reduced by ethosuximide, specific for control of absence seizures

Psychiatric Disorders in Epilepsy

A.Disorders due to brain damage also causing seizures:

Neurodegenerative disorders e.g. Alzheimer's disease

Focal brain injury e.g. tumour, head injury

Neurodevelopmental syndromes e.g. infantile spasms, Lennox Gastaut, tuberous sclerosis

B.Disorders related to seizures:

Pre-ictal prodromata e.g. mood change, irritability

Ictal events e.g. auras of complex partial seizures

Post-ictal e.g. twighlight states

C. Inter-ictal disorders:

Personality disorders

Epileptic psychoses

D. Pseudoseizures

Temporal Lobe Personality Syndrome

Emotionality

Elation and euphoria

Sadness

Anger

Aggression

Altered sexual interest

Guilt

Hypermoralism

Obsessionalism

Circumstantiality

Viscosity

Sense of personal destiny

Hypergraphia

Religiosity

Philosophical interest

Dependence

Humourlessness

Paranoia

Differentiated patients with TLE from other neurological patients and normal controls

Ideative components distinguished left sided lesions

Emotional components distinguished right sided lesion

N.B. Other studies have not replicated this finding when controlling for other forms of epilepsy

and presence or absence of psychiatric disorder

TLE and Aggression

During an automatism

Inter-ictal aggression: 33% lobectomy patients

teenage males

L focus

improvement of seizures and aggression following surgery

Epileptic Psychoses

A. Directly related to seizures

petit mal status

twiglilight states

B. Inter-ictal

transient schizoaffective or affective states affective psychoses

chronic schizophreniform state

Inter-ictal Schizophreniform Psychosis

10-15% poorly controlled TLE receive diagnosis of schizophrenia or schizophrenia

left sided focus

69 patients with unequivocal epilepsy and subsequent diagnosis of epilepsy psychosis mean of 14 years following onset of epilepsy

no family history or history of schizotypal personality traits

brain damage in 50%

most had TLE

no relation with severity or medication

schizophrenia like symptoms: paranoid delusions (100%), thought disorder (50%), auditory hallucinations (46%), thought insertion and thought block

unlike schizophrenia: rnystical or religious content, visual hallucinations (16%), warm affect, personality well preserved, good social function

Pseudoseizures

(psychogenic seizures, hysteical seizures non-epileptic seizures

Up to 20% of referrals

Unlikely to occur in who have not experienced true epilepsy (contentious)

History of frequent hospital admissions and social problems

Current or past history of psychiatric disorder esp. depression

History of attempted suicide

Sexual maladjustment

History of extreme childhood abuse (10-15%)

Organic brain disease inc mental retardation

Clinical features:

out-of phase limb movements

side to side head movements

pelvic thrusting

no post-ictal neurological signs

no incontinence of self harrn

prolactin levels not raised

N.B. can be difficult to distinguish from frontal-lobe seizures

Study of 47 cases of pseudoepilepsy

unresponsive behaviour absence of motor manifestations most common

pelvic thrusting, side to side head movements, out-of phase movements uncommon

most treated with anticonvulsants

6 mistaken for status epilepticus (slow writhing and in-phase movements)