Neurotransmission going wrong - Epilepsy

Question 1

What are the different types of neurotransmitter?

Answer 1

Acetylcholine, amino acids, biogenic amines, peptides, and unconventional

Question 2

Which receptors does acetylcholine act on?

Answer 2

Nicotinic (ion channel) receptors and muscarinic (GPCR - metabotropic)

Question 3

Give some examples of amino acid neurotransmitters and the receptors they act on

Answer 3

Glutamate - main excitatory in CNS. GABA - main inhibitory in CNS. The glutamate receptors are NMDA, AMPA, kainate (ionotropic) & mGluR (metabotropic). GABA receptors are GABAa,b which are ionotropic and metabotropic. Aspartate and glycine are excitatory and inhibitory neurotransmitters also

Question 4

Name some biogenic amines and how they act

Answer 4

Adrenaline, noradrenaline, dopamine (catecholamines), serotonin, histamine. They’re involved in many CNS and PNS pathways affecting aspects of behaviour, movements, and homeostasis. Many psychoactive drugs act by regulating their activities

Question 5

Name some peptides and their activities in the nervous system

Answer 5

Endorphins (endogenous opioids), substance P. Involved in emotion regulation, pain perception, stress response

Question 6

What are some “unconventional” neurotransmitters?

Answer 6

Nitric Oxide, which crosses membranes affecting cGMP, and endocannabinoids which are lipids that bind to opiate receptors

Question 7

What is the role of ATP in neurotransmission?

Answer 7

ATP is often released with other neurotransmitters, but has it’s own neurotransmitter properties, acting on purinergic receptors

Question 8

What is the mechanism of action of neurotoxins?

Answer 8

They often block the NMJ, leading to paralysis, and hence suffocation

Question 9

What is the definition of epilepsy?

Answer 9

A disease characterised by recurring seizures occuring spontaneously and unpredictably

Question 10

What is a seizure?

Answer 10

A transient occurrence of signs &/or symptoms due to abnormal or synchronous neuronal activity in the brain

Question 11

What is an EEG?

Answer 11

An electroencephalography, records electrical activity in the brain, detecting signs of neurological dysfunction

Question 12

What is symptomatic epilepsy?

Answer 12

It is epilepsy associated with anatomical/pathological abnormalities and/or clinical features indicative of an underlying disease or condition such as brain injury, infections eg. meningitis, stroke, tumour. Includes developmental disorders

Question 13

What is idiopathic epilepsy?

Answer 13

Epilepsy with unknown cause, responsible for 60-70% of cases. The origin is though the be genetic but only a small number of cases are due to a single mutation

Question 14

How can an EEG be used to diagnose epilepsy?

Answer 14

It records abnormal electrical activity in brain via electrodes on the scalp. The waves and spikes on each line (per electrode) show the sum firing of cortical neurons. A greater amplitude of signal = neuronal activity is more synchronous. An EEG measures the sum PSP of neurons around the electrode area. It can measure activity after an event (event-related potential) or just activity in general

Question 15

Describe the neuronal activity that occurs during a seizure

Answer 15

Neurons in the epileptogenic zone (a cortical region capable of generating a seizure) discharge hypersynchronous action potentials at a high rate and/or in an abnormal pattern.

Question 16

Which areas can seizures originate in?

Answer 16

Seizures can only originate in the cortex of frontal, parietal, occipital, and temporal lobes. They may spread to other regions.

Question 17

What is a partial/focal seizure?

Answer 17

A seizure that starts locally, accounts for about 60% of cases. Either simple partial or comlex partial

Question 18

Describe what is meant by a simple partial seizure.

Answer 18

They are partial seizures that involve no loss of consciousness. Their effects depend on the area of the brain they are active in.

Question 19

What is a simple motor seizure?

Answer 19

A seizure that manifests as muscle contractions. Caused by a lesion in the motor cortex (precentral gyrus) of the contralateral cerebral hemisphere. Can be sustained (tonic) or intermittent (clonic) and can involve any body part

Question 20

What is a simple somatosensory seizure?

Answer 20

Manifests as tingling/pins and needles. Caused by a lesion in/near somatosensory cortex (postcentral gyrus) of contralateral cerebral hemisphere

Question 21

What is a simple visual seizure?

Answer 21

Manifests as spots/patterns in the visual field. Caused by a lesion in/near occipital lobe (visual cortex) contralateral to the affected visual field

Question 22

What other sensations can be affected by seizures?

Answer 22

Auditory, vestibular, olfactory, visceral

Question 23

What is a complex partial seizure?

Answer 23

A partial seizure that affects consciousness, usually arises from epileptogenic zones in hippocampus, parahippocampal area, or amygdala - deep temporal lobe structures

Question 24

Describe the progression of a complex partial seizure

Answer 24

Usually the first phase is an “aura” - illusion, hallucination, altered cognitive state, or an experience like those caused by simple partial seizure. Next phase is the alteration of consciousness, often with dystonic (stiff/twisted) posturing of limbs

Question 25

What is a generalised seizure and what are the two different types?

Answer 25

A seizure involving abnormal electrical activity widely across both hemispheres from onset. Convulsive (tonic-clonic) and non convulsive: absence, atonic, myoclonic

Question 26

What is the cause of a tonic clonic seizure?

Answer 26

There is a fast rhythmic discharge (>10Hz), decreasing in freq. and increasing in amplitude. The switch from continuous to intermittent bursts of activity signal the beginning of the clonic phase. The intermittent bursts of activity are called grouped polyspikes and they are separated by quiet intervals. They gradually decrease in frequency as do the repetitive clonic muscular jerks

Question 27

Describe what is meant by an absence seizure (petit mal)

Answer 27

A seizure that involves an interruption to consciousness where the person becomes vacant and unresponsive for a short while (up to 30s)

Question 28

What causes absence seizures?

Answer 28

Abrupt onset and cessation of bilaterally synchronous regular “spike and wave” discharges (3Hz) over widespread areas of the scalp

Question 29

Describe what is meant by an atonic seizure

Answer 29

The loss of postural muscle tone. In a mild form, the head will drop as if unsupported. A sever seizure would be all postural muscles relaxing and the patient collapses. The attack only lasts for a few seconds but the seizure may be longer

Question 30

Describe what is meant by a myoclonic seizure

Answer 30

A seizure involving brief involuntary muscle jerks occuring singly or in a brief salvo of repeated jerks. Can be one muscle or whole groups. Repetitive massive myoclonic jerks occur with no alteration in consciousness

Question 31

What is status epilepticus?

Answer 31

A state of continuous seizures (or intermittent without regaining consciousness). The limit is 5 mins. It is a major neurological emergency with a mortality rate of about 30%. Can lead to permanent CNS damage, often hippocampal lesions with memory loss and confusion

Question 32

How do seizures start?

Answer 32

A change in excitatory and inhibitory neurotransmission balance can result in a hyperexcitable state, inducing a seizure. This can happen by increased excitatory neurotransmitter input, decreased inhibitory neurotransmitter input, alterations to connectivity (synapse sprouting) or NA+/Ca2+ channel activation

Question 33

What is the main principle behind antiseizure drugs?

Answer 33

They modify the ion channel, receptor, or synapstic processes to favour inhibition over excitation in order to reduce/prevent seizures.

Question 34

How do Na+ channel blockers work as anti seizure drugs?

Answer 34

They do not allow the ion channel to return to the resting state after the inactive state (refractory period), thereby stabilising the inactive state. This prevents repetitive firing but doesn’t affect normal transmission.

Question 35

How do Ca2+ channel blockers work as anti seizure drugs?

Answer 35

They inhibit the T type calcium channels which are activated at low voltage (as opposed to L, P/Q, and N type). These channels conduct a small and transient current but since they only need a small depolarisation to open, they affect neuronal excitability. They cause a Ca2+ spike which leads to further depolarisation and bursts of action potentials leading to seizures. Inhibiting these channels can control absence seizures

Question 36

How do GABA enhancers work as anti seizure drugs?

Answer 36

GABA + its A receptor leads to opening of Cl- channels, hyperpolarising the neuron. GABA enhancers can work in many ways eg. blocking uptake transporter, blocking metaboliser

Question 37

How can glutamate blockers work as anti seizure drugs?

Answer 37

Glutamate binds to several post synaptic receptors. AMPA is involved in fast excitatory transmission. Glutamate blockers can block AMPA and NMDA receptors, and also enhance removal of glutamate from the synapse, and interfere with the release of glutamate from the vesicle in the pre synaptic neuron

Question 38

What are some alternatives to pharmacological treatments for seizures?

Answer 38

In about 30% of cases, drugs don’t work. Surgery used to remove a lesion (tumour, blood clot), or resect white matter tracts to stop spread. Ketogenic diet mimics biochemical adaptations to fasting which can be good for seizures. Deep brain stimulation (to increase inhibitory mechanisms) and stem cell therapies are currently being studied.