Headaches and Epilepsy Flashcards

1
Q

4 types of headaches

A

Tension, cluster, migraine, sinus

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2
Q

Primary headache

A

Headaches are classified as either primary (when they are not caused by something else).
A primary headache is likely due to pain sensing nerves, muscles, blood vessels, or changes in chemical activity:
migraines, tension, and cluster headaches are good examples.

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3
Q

How do we treat tension headaches

A

Most are easily treated with over-the- counter (OTC) medications, including:
• Aspirin, ibuprofen or paracetamol
• Daily prescription medications, including tricyclic antidepressants, may manage tension-type headaches.
Alternative therapies aimed at stress reduction may help. They include:
• Meditation, relaxation training
• Cognitive behavioural therapy
• Biofeedback
• Massage and gentle neck stretches
• Heat therapy (warm compress or shower)

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4
Q

What causes migraines

A

Migraines may be caused by changes in the blood vessels of the brain stem and their interactions with the trigeminal nerve.
Imbalances in serotonin, which helps regulate pain, may be involved.
Serotonin levels may decrease during a migraine - this causes the trigeminal nerve to release neuropeptides, which come into contact with the meninges, resulting in migraines.
Triggers: stress, fatigue, anxiety, changes in altitude, hormonal changes, environmental changes

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5
Q

How do we treat migraines

A

Migraine treatment is aimed at relieving symptoms and preventing additional attacks.
Treatments may include:
• Rest in a quiet, dark room
• Hot or cold compresses to your head or neck
• Massage and small amounts of caffeine
• Over-the-counter medications such as ibuprofen, paracetamol, and aspirin
Prescription medications such as triptans, e.g. sumatriptan and zolmitriptan (serotonin agonists) which cause cranial vasoconstriction, reduce blood flow and inflammation.
Preventive medications, e.g. propranolol (beta blockers which dilate blood vessels – unclear how this helps!), amitriptyline (TCA) or topiramate (antiseizure).

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6
Q

Secondary headaches

A

Secondary headaches are caused by something else, which activates the pain-sensing nerves of the head. Thus, headaches can be a symptom of something very serious, and if headaches are persist, increase in intensity, or are regular, they should be checked.
A wide range of possible causes with varying severity.
Causes of secondary headaches: dehydration, concussion, influenza, glaucoma, meningitis, brain aneurysm

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7
Q

What is epilepsy

A

Group of >55 subtypes of disease characterized by unprovoked and provoked recurring seizures. A seizure is hypersynchronous hyperexcitability of groups of neurons, starting from a focus. The membrane potential of these cells may be more depolarised than usual, meaning they fire action potentials more readily.
Diagnosis by EEG

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8
Q

Seizure classification

A

Seizures can be:
Generalized (involving both cerebral hemispheres and is often a genetic disorder): tonic, clonic and absence

Partial (focal): simple partial and complex partial
(simultaneous firing of a group of neurons “epileptic focus“)
- often caused by focal trauma (acquired epilepsies)

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9
Q

Generalised seizures: tonic - conic (grand mal)

A

• Tonic phase: (tonic seizures consist of strong contraction of whole body musculature – all muscles stiffen)
– initial strong contraction of whole musculature, cry or groan, loss of consciousness, stop of respiration; salivation, sometimes loss of bladder (rarely bowel) control

• Clonic phase:
– violent, synchronous jerks (clonic seizures), can last several minutes
• Injuries can occur (from objects around the seizing patient, tongue biting, falling)
• Slow recovery (regaining of consciousness), confusion, drowsiness
• Tonic or clonic seizures can occur by themselves as well.

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10
Q

Generalised seizure: absence seizures (petit mal)

A
• Typically in childhood or teens
• Sudden loss of consciousness, but
intact control of musculature
• Usually short (1-15 sec); recurs often
(up to hundred times);
  • Symptoms: staring, fluttering of eyes, during longer seizures: automatisms (such as lip smacking, picking at clothes, fumbling);
  • Patient then resumes previous activity
  • Amnesia; no recollection of event.
  • It is as though the youth is „absent“ for a few seconds.
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11
Q

Partial seizure

A

Focal seizures are initiated by simultaneous firing of a group of neurons in the brain (epileptic focus).
– The site of pathological discharge determines the symptoms (e.g. motor vs. sensory cortex).
– Focal high-frequency discharges of impulses can spread to other areas in the brain (generalisation) and whole body can get involved.

Simple partial:
Preserved awareness, memory & consciousness

Complex Partial: If any of the above are impaired.
Most common in adults.

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12
Q

Partial seizures - causes?

A

– anoxia or hypoglycemia during and after birth
– infections (meningitis), fever (in children)
– brain trauma (in young adults, accidents)
– drug abuse (e.g. cocaine overdose, withdrawal from ethanol in alcoholics)
– lack of sleep, flashing lights
– tumours, stroke
– drugs: theophylline/ caffeine, amphetamines, penicillin
– often unknown causes

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13
Q

Simple partial seizures

A

Signs and symptoms:
Frontal lobe - motor signs such as twitching or stiffness
Parietal lobe - burning/tingling/numbness
Occipital lobe - visual disturbances/hallucinations
Temporal lobe - deja vu, unusual taste/smell, feeling of fear

The partial seizure experience depends on the seizure focus and the extent of the seizure spread.
• Motor seizures – within motor cortex or processing centres;
• Sensory seizures: abnormal gustatory, olfactory, auditory, visual sensations – odd sensations, etc.

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14
Q

Complex partial seizure

A
  • Consciousness impaired during seizure but postural control retained
  • … most often originate in temporal lobe (e.g. hippocampus, amygdala)
  • Stereotypical behaviour during seizure, post-seizure amnesia: don‘t remember seizure
  • Often resistant to drug treatment.

Impairment of consciousness: cognitive, affective symptoms
Dreamy state, blank, vacant expressions
Formed auditory hallucinations (hears music)
Formed visual hallucinations (sees house/tree that isn’t there)
Olfactory hallucinations: bad/unusual smells
Psychomotor phenomena: chewing movements, wetting lips, automatisms
Dysphasia

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15
Q

Status epilepticus (SE)

A

One continuous seizure for > 30 minutes or 2 or more sequential seizures without full recovery of consciousness

Convulsive SE: life threatening – mortality ~ 30 %
̈ Children lower mortality
̈ Elderly up to 80% mortality

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16
Q

Mechanisms of action of antiepileptic drugs:

How can we reduce hyperexcitability?

A
  1. Blockade of sodium channels which are required for
    impulse transmission
  2. Blockade of presynaptic calcium channels
    3.Strengthening of inhibitory (GABAergic) input
  3. Blockade of excitatory (glutamatergic) input
17
Q
  1. Blockade of sodium (Na+) ion channels
A

Several states:

  • Closed (resting)
  • Open
  • Inactivated
  • Antiepileptic drugs (AEDs) bind preferentially to inactivated state and thus inhibit rapid firing
  • Normal function of Na channels remains; very clever selective block

Drugs: Carbamazepine, Phenytoin, Valproate, Lamotrigine

18
Q
  1. Block of pre-synaptic calcium (Ca2+) ion channels
A
  • Action potential triggers voltage-gated Ca2+ channels to open in the presynaptic terminal;
  • The influx of Ca2+ triggers the fusion of the synaptic vesicles with the plasma membrane, releasing neurotransmitters into the synaptic cleft.
  • Blocking of calcium ion channels can reduce release of neurotransmitter and slow synaptic function.

Drugs: Ethosuximide, Pregabaline, Gabapentin, Valproate

19
Q
  1. Increase GABAergic transmission
A
  • Binding of GABA by GABAA receptors induces opening of receptor pore, influx of chloride and hyperpolarization, which reduces membrane potential and reduces Aps
  • Benzodiazepines and barbiturates are allosteric modulators of GABAA receptors

Drugs: diazepam, clonazepam (used to stop SE), phenobarbital

20
Q
  1. Reduce glutamate activity
A

Seizures can be caused by overactivation of ionotropic glutamate receptors; glutamate is excitatory.

Four families of receptors: 1)AMPA and 2) kainate receptors (excitatory cation channels)

3) NMDA receptors
(excitatory with high Ca2+ permeability)

4) Metabotropic receptors
(can be excitatory or inhibitory)

Drugs:
- AMPA/KA-R blockade (topiramate)

21
Q

Classical and New antiepileptic drugs (AEDs):

A

Classical
• Phenytoin • Ethosuximide • Carbamazepine •Valproicacid • Phenobarbital • Benzodiazepines

New (since 1993)
• Gabapentin • Lamotrigine • Topiramate • Tiagabine
• Levetiracetam • Pregabalin

22
Q

Pharmacodynamic properties of classical AEDs

A
  • Narrow therapeutic index: the concentration difference between therapeutic effects and toxicity is very small.
  • Patients may experience CNS depression reflected in sleepiness, dizziness, ataxia …

• Hypersensitivity reactions
– rare but present with most AEDs
– often manifest as skin reactions or hematotoxicity

• Teratogenicity
– e.g. valproic acid, phenytoin, carbamazepine; continue through pregnancy?

23
Q

Pharmacokinetic properties of classical AED: how the body metabolises the drugs

A

• Long half-lives (>12hrs), effective dose management may be difficult

• Modulation of cytochrome P-450 enzyme activities
– Induction by phenobarbital, phenytoin, carbamazepine
– Inhibition by valproicacid
– Requires dose adjustments and causes interactions with other drugs

  • Poor patient compliance
  • Therapeutic drug monitoring (TDM) recommended
24
Q

Classic AED: Phenytoin (PHT)

A

Classic AED, still first-line drug for partial sz; also used for generalized convulsive seizures; not useful for absences sz

MOA: use-dependent sodium channel blockade

PHT induces P-450 isozymes and actually increases its own metabolism

Half life = 20h (but increases with higher doses)

TDM is highly recommended!

Induction of cytochromes P-450 causes increased metabolic breakdown of other drugs (contraceptives)

25
Q

Phenytoin: adverse effects

A

Dose-related functional neurotoxicity:
– Nystagmus, ataxia, dizziness, sedation, confusion

  • Allergic reactions including skin rashes, hematologic problems
  • Typical with long-term use: – Gingival hyperplasia

• Teratogeniceffects
– skeletal, CNS, limb and orofacial malformations

26
Q

Classic AED: Carbamazepine (CBZ)

A

• Useful for focal and generalised epilepsies (1st line drug)

– MOA use-dependent blockade of sodium channels

• Used also for migraine and trigeminal neuralgia, chronic (neuropathic) pain, mood stabilizer, etc.

CBZ induces its own metabolism by induction of CYP3A4

Adverse Effects:
– Sedative actions – Allergic reactions – Teratogenic

27
Q

Classic AED: Valproic acid / Valproate

A

• Useful for most types of partial and generalized epilepsies including absences and myoclonic sz
– drug of choice for unclassified forms
• MOA poorly characterized. Na and Ca channel blocker, inhibitor
of GABA breakdown (GABA transaminase)
• Long plasma half life 15 h, inhibitor of cytochrome P-450
• Adverse effects:
– Nausea, vomiting, anorexia, but also significant weight gain – Minimal sedation compared to other classical AED
– Allergic reactions possible (hematotoxicity)

28
Q

New AED: Lamotrigine

A
  • New AED approved for monotherapy
  • for partial sz, absence and generalized tonic-clonic seizures
  • MOA: Na+ channel blocker
  • PK: Slow titration schedule, metabolized by liver, not an enzyme inducer, little interaction with other drugsJ
  • Few adverse effects compared to classic drugs
  • However, it can be teratogenic: risk for oral clefts doubled if used during pregnancy.
29
Q

New AEDs: Gabapentin - Pregabaline

A
  • GABA analogues blocking calcium channels but not clear?
  • Effective for partial seizures
  • Less severe sedation/ataxia (lack of voluntary control of muscle movements) than older drugs
  • No drug - drug interactions
  • Both drugs about 6 h half life
  • Used also for neuropathic pain
30
Q

What are the main targets used by drugs to treat epilepsy? How do these reduce excitability?

A

Blockade of sodium channels, presynaptic calcium channels, excitatory input and strengthening inhibitory input.

31
Q

What are some problems of older anti-epileptic drugs? Why are newer anti-epileptic drugs generally better?

A

Classic AEDs have a narrow therapeutic index, patients may experience CNS depression, hypersensitivity reactions and teratogenicity.

Newer AEDs have little interaction with other drugs and few adverse effects compared to classic drugs. They have decreased sedation and improved pharmacokinetic profile.

32
Q

How do we treat primary headaches, generally? How do migraine headaches differ from “normal headaches”?

A

Primary headaches are generally treated with OTC medications and alternative therapies that reduce stress.

Migraines can occur when serotonin levels in the brain decrease and can have much more severe and intense symptoms than normal headaches. Treatment includes resting, massaging, caffeine, OTC/prescription and preventative mediations. Migraines can be caused by stress, fatigue, environmental factors, hormones…