Migraine

Mea Cerebrum Nocet….

History of Presenting Illness

Typically, a throbbing pulsating pain
intensifies with any activity
nausea + vomiting = common
visual or audial AURA preceding onset of pain:
develops over 5-20 minutes and lasts less than 60 minutes.
Less commonly: phonophobia and photophobia
Differential Diagnoses

Also consider Transient Ischaemic Attack, ruptured intracranial aneurism and brain tumour
History
Important features:
Age at onset ==Red Flags==
Location(s)- usually unilateral - Decreased consciousness
Frequency - Confusion
Duration - Seizures
- History of head trauma
Character
- Fever
Intensity - Neck stiffness
Mode of onset (aura?) - Papilloedema
Associated symptoms - Focal neuro deficit eg.
(neurologic, gastrointestinal, sensory) hemiparesis (could still be a
Family history of headache migraine, but a sinister sign
Known or suspected precipitating factors (triggers) nonetheless
Aggravating and ameliorating factors
Prior and current medications Migraine Symptom vs.
Patients Affected, %
Relation to menstrual cycle:
Headaches tend to occur in relation to the menstrual cycle. This is Nausea 87
especially true of headaches that begin happening in the early Photophobia 82
teenage years or after pregnancy. Lightheadedness 72
Stress and lack of sleep Scalp tenderness 65
Intake of caffeine, chocolate, red wine, food additives Vomiting 56
Vasoconstrictors precipitate migraine directly. Visual disturbances 36
Caffeine is one such sympathomimetic vasoconstrictor agent. Tyramine and Photopsia 26
phenylethylamine are vasoconstrictors present in red wine, aged cheese, Fortification spectra 10
and dark chocolate Paresthesias 33
Vasodilator agents precipitate migraine through an indirect mechanism. Vertigo 33
Culprit food additives: Alteration of consciousness 18
sodium nitrite (preservative) Syncope 10
Seizure 4
Monosodium Glutamate
Confusional state 4
Aspartame (artificial sweetener) Diarrhea 16
History of head trauma
Results of any prior neuroimaging

Precipitating factors
Examination
in migraine: IF your patient has “uncomplicated” migraine, neurological examination will be all clear.
- precipitous falls in
oestrogen levels
HOWEVER: the key is to rule out anything horrible eg. space-occupying lesion
(i.e. menstrual) THUS:
- chronic stress - scope the fundus for papilloedema + retinal haemorhages
- fatigue - (also a good assessment of peripheral vascular disease)
- anxiety - look for neck stiffness to rule out intracranial infection
- alcohol
- perform a neurological exam to make sure there is no persisting neuro deficit
- strong smells
- post-exercise - (if there is something like hemiparesis or blindness, it may be still due to a
- intense heat or migraine- but now you would call it “complicated migraine”, see definitions below)

-
bright light
certain food stuffs Tests and Investigations
- hypertension IMAGING is indicated IF:
- sinusitis First or worst headache of the patient's life
-
- cervical Change in frequency, severity, or clinical features of the headache
-
spondylosis
Abnormal neurological examination
-
- some intracranial Progressive or new daily, persistent headache
-
diseases.
-
Neurological symptoms that do not meet the criteria for migraine with typical aura or
that themselves warrant investigation
- Persistent neurological deficit
- Hemicrania that is always on the same side and associated with contralateral neurological symptoms
- Inadequate response to routine therapy
- Atypical clinical presentation
MRI is the modality of choice for this sort of thing.
SEROLOGY would be useful for monitoring therapeutic drug levels and to rule out metabolic disturbances
LUMBAR PUNCTURE is to be avoided unless there is good reason to think its MENINGITIS
Disease Definition
International Headache Society Criteria for Migraine (and some other common headaches)
Migraine without aura (MO) diagnostic criteria Migraine with aura (MA) diagnostic criteria
A. At least five headache attacks lasting 4 - 72 hours A. At least two attacks fulfilling with at least three of the
(untreated or unsuccessfully treated), which has at least following:
two of the four following characteristics: 1. One or more fully reversible aura symptoms indicating
1. Unilateral location focal cerebral cortical and/or brain stem functions
2. Pulsating quality 2. At least one aura symptom develops gradually over
3. Moderate or severe intensity (inhibits or prohibits daily more than four minutes, or two or more symptoms occur in
activities) succession
4. Aggravated by walking stairs or similar routine physical 3. No aura symptom lasts more than 60 minutes; if
activity more than one aura symptom is present, accepted
B. During headache at least one of the two following duration is proportionally increased
symptoms occur: 4. Headache follows aura with free interval of at least 60
1. Phonophobia and photophobia minutes (it may also simultaneously begin with the aura
2. Nausea and/or vomiting B. At least one of the following aura features establishes a
diagnosis of migraine with typical aura:
1. Homonymous visual disturbance
2. Unilateral paresthesias and/or numbness
3. Unilateral weakness
4. Aphasia or unclassifiable speech difficulty
BELOW is stuff that can be safely ignored, as it
is slightly beyond the scope of this case
Cluster Headache
A. At least five attacks of severe unilateral
orbital, supraorbital and/or temporal pain lasting
15 to 180 minutes untreated, with one or more
of the following signs occurring on the same
side as the pain
1. Conjunctival injection
2. Lacrimation
3. Nasal congestion
4. Rhinorrhoea
5. Forehead and facial sweating
6. Miosis
7. Ptosis
8. Eyelid oedema
B . Frequency of attacks from one every other
day to eight per day
Tension-Type Headache
A. Headache lasting from 30 minutes to seven
days
B. At least two of the following criteria:
1. Pressing/tightening (non-pulsatile) quality
2. Mild or moderate intensity (may inhibit, but
does not prohibit activity
3. Bilateral location
4. No aggravation by walking, stairs or similar routine physical activity
C . Both of the following:
1. No nausea or vomiting (anorexia may occur)
2. Photophobia and phonophobia are absent, or one but not both are present
Cervicogenic Headache
A. Pain localised to the neck and occipital region. May project to forehead, orbital region, temples, vertex or ears
B. Pain is precipitated or aggravated by special neck movements or sustained postures
C . At least one of the following:
1. Resistance to or limitation of passive neck movements
2. Changes in neck muscle contour, texture, tone or response to active and passive stretching and contraction
3. Abnormal tenderness of neck muscles
D. Radiological examination reveals at least one of the following
1. Movement abnormalities in flexion/extension
2. Abnormal posture
3. Fractures, congenital abnormalities, bone tumours, rheumatoid arthritis or other distinct pathology (not spondylosis or osteochondrosis)

There are 4 subtypes which one must recognise:

- Complicated Migraine: one which features a persistent neuro deficit
- Uncomplicated Migraine: one where the neuro signs disappear together with the pain
- Common Migraine is the 70% of migraine which is not preceded by an aura
- Classical Migraine is always preceded by an Aura.
Also there are Migraine Equivalents, i.e aura symptoms which occur without a following headache
How do you know its not something else:
1. By VISUAL and SENSORY AURA SPREADING RATE:
Unlike TIA, the migraine aura (so-called “scintillating scotoma”) spreads
slowly, over 20 minutes up to 1 hour.
TIA symptoms reach their maximal manifestation in fewer than 5 minutes
2. By its location: migraine is typically unilateral
3. By its duration: gradual onset, peaking within 2 hours;
!! Super-rapid onset headaches justify panic and immediate investigation !!

Management from NEJM 2002

ACUTE: !! In the US, 50-80% of patients with chronic daily headaches reported analgesic overuse

With DRUGS: acute attack

The drug should be taken as soon as the headache component of the attack is recognised
- ASPRIN
- PARACETAMOL Rubbing temples seems to help: ? by inducing extracranial artery
vasoconstriction, thus reduced stretch receptor signalling ?
- IBUPROFEN
- Any combination of the above
- PLUS you may want to take an antiemetic if nausea is a problem; its important to be able to digest
the drugs above without throwing them all back up.
!! AVOID OPIATES !! or your patient may look like (or be) an addict when he/she switches GPs
plus, opiates ONLY MASK the pain, without treating the pathophysiological basis of the attack

Ergot Derivatives: low cost and long experience in the field: BUT awful side-effects
Eg. nausea, vomiting, cardiac ischaemia, persisting peripheral vasoconstriction, and
ergotism which is a horrible convulsive illness (spasm of arterioles with thrombosis and
gangrene caused by ergot poisoning, aka. St Anthony’s Fire) which historically has been
confused with demonic possession and manifestations of witchcraft.
Such as: ergotamine and dihydroergotamine
Ergot compounds work by
- Vasoconstriction everywhere
- Reducing the release of neurogenic inflammatory peptides

Tryptamines (tryptans): unlike ergot compounds, these actually have EBM

prescription instructions of dosage etc; they also have well-established
pharmacokinetics and a nice comforting safety record.
Such as sumatriptan, naratriptan, rizatriptan, zolmitriptan, and almotriptan
Triptans work by
- Selectively vasoconstricting cranial arteries via 5-HT 1b and 1d receptors
- Inhibiting neurotransmission in trigeminal pain (spinal) nucleus via same receptors
- Inhibiting release of neurogenic inflammatory peptides, same mechanism
PROPHYLACTIC:
Treatments to date are relatively nonspecific, their efficacy is moderate, and they have substantial side effects.
Suggestions is that prophylactic migraine drugs somehow block cortical spreading depression.

5-HT 2a and 2c receptor antagonists: eg. pizotifen, methysergide

side effects: increased appetite, weight gain, sedation.
Work by blockading vasoconstriction and platelet aggregation, thus reducing spreading cortical hypoperfusion
Beta-1 Adrenoceptor Blockers also seem to have some effect by unknown mechanisms
Tricyclic antidepressant AMITRIPTYLINE has proven effect –
- Once again, nobody knows how or why.
Sodium Valproate, an anticonvulsant, also has a proven effect – but no other anticonvulsants
Happily, there is no biopsychosocial treatment for this condition.
AVOIDANCE OF TRIGGERS: important if coffee or chocolate produces your migraine
= this is quite common; Roger Pamphlett is one example
Prognosis:
Every person responds differently to treatment. Some people have rare headaches that require little to
no treatment. Others require the use of several medications or even occasional hospitalisation.
Most people who develop migraines will continue to have intermittent headaches over
many years. Migraines often end when people reach their 50s or 60s.

Epidemiology
= the most common cause of vascular headache,
afflicts approximately 15% of all women and 6% of all men
Risk factors:
- Being mid-menstrual
st
- Being pregnant, in the 1 trimester
- Having a family history ( over half of cases may be inherited)
- Weak association with asthma and allergy
- Weak association with epilepsy
- Some personality factors, eg. over-responsiveness to stress

BIOPSYCHOSOCIOCULTUROPHILOSOPHICAL aspects
Headache and Emotional Distress in the Community (LT)
headache is a common presenting complaint in general practice.
The two commonest headache syndromes are migraine and tension headache.
TENSION classified into
episodic (occasional) and
chronic (daily) tension headache on the basis of their time course.

Both syndromes may be associated with emotional distress.

People with migraine are more likely than others to suffer clinical depression, and people with a
history of depression are more likely to have a history of migraine.

Strongly felt emotions eg. depressive symptoms
potential precipitant of an episode of headache.

headache is a not-uncommon presentation of depression in general practice.

Presentation like this, of a physical symptom reflecting mental disorder, is called 'somatization'.

Tension headaches associated with depression tend to improve as the depressive

illness responds to treatment.
 Pathophysiology: a possible MECHANISM OF MIGRAINE
NOXIOUS STIMULUS
- Increased Amino Acids in CNS ECF
- Increased K+, thus induced depolarisation Cortical Spreading Depression
- Glutamate NMDA receptor agonists Brief excitation, followed by 10 minutes of
- Reduced Mg++, thus increased NMDA activation inhibition of neuronal activity:
- Mechanical stimulus FIRST @ OCCIPITAL LOBE
- Coffee, chocolate, red wine, cheese Spreading at 2 – 6 mm per minute
- Depression

Occipital excitation Dysfunction of neurones which control cortical blood flow

= AURA
-
Transient depolarisation of fibres which control sub-pial arteriole diameter

??? PARADOXICAL HYPEROXIA ??? VASCULAR CHANGES:

seen on PET scans: possibly due to reduction in neuronal activity during HYPOPERFUSION ! Not hypoxia !
the 10 minute inhibition
THUS possibly less demand for oxygen and thus more oxygen in the = Change in peripheral resistance (increases!)
ECF and capillaries?… speculation only! THUS: responsive increase in
diameter of pain-sensitive intra and
SWOLLEN, extra-cranial ARTERIES
PULSATILE DISTORTING
qualities of STIMULUS:
headache conveyed - Vasodilation
by the blood - Stretching
vessels: - Local Inflammation Stretch Receptors
-

Afferent trigeminal
pain fibres

Trigeminal ganglion

SPINAL TRIGEMINAL
NUCLEUS
THALAMUS Cross to Signal transduced and
contralateral transmitted
* Reflex arcs work here
Ventro-Posterior Medio-Dorsal MEDULLA: MIDBRAIN:
Thalamus Thalamus Reticular Mesolimbic +
= point-for-point = links to cingulate
representation of formation mesocortical
= ? depression? = somatic and
bodily areas;
project to
behavioural
hypothalamus
THUS: integration of responses to pain,
= Autonomic and
pain with normal “suffering”
endocrine
tactile sensation responses; eg.
crying, anorexia,
?insomnia
Cingulate and
Prefrontal Medial
cortexes:
= EMOTIONAL
RESPONSE
= modification of
motivational states
(eg. hunger and
pain)
 Basic Sciences: Relevant anatomy
Superficial
temporal Middle cerebral Inf saggital temporal
sinus
Circle
of Willis Anterior cerebral Cavernous Sinus
Sup
saggital
ophthalmic
Carotid maxillary
canal Great
central vein
Post. of Galen
cerebral maxillary
Straight
basilar sinus

Occipital Rt transverse facial

sinus
facial
Occipital sinus
Int.carotid
lingual Occipital vein
External carotid Sigmoid sinus
vertebral
Carotid Vertebral vein
thyrocervical sinus Ext. Jugular vein Int. jugular

Common carotid subclavian

brachiocephalic
subclavian

Axillary brachiocephalic
clavicle
Sup. vena cava
Internal thoracic
First rib clavicle axillary Int. thoracic
Second rib
Sup saggital sinus
Roots of sup.
cerebral veins

Ant cerebral

Internal
carotid Ant communicating mid cerebral
vein
mid Ant cerebral
cerebral
post communicating Pontine
Pituitary vein
post cerebral
gland
Petrosal
vein
basilar
Sup cerebellar Inferior
cerebral
veins
pontine

labyrinthine

AICA
vertebral Inf cerebellar veins
Petrosal sinus
PICA
Ant spinal
Straight sinus Transverse
sinus
Occipital sinus
internal carotid artery
- supplies blood to the majority of the cerebral cortex; enters cranium next to optic chiasm
1st branch: posterior communicating artery
2nd branch: anterior choroidal artery:
- supplies limbic region:
choroid plexus of the lateral ventricle (hence its name), the internal capsule (the retro-lenticular limb), hippocampal formation and amygdala

Then:
int.carotid divides into 2 major branches: MIDDLE and ANTERIOR CEREBRAL arteries
anterior cerebral artery : medial surface of frontal and parietal lobes + parts of pre- and post-central gyri containing somatotopic
representation of the lower limb). Its cortical supply also extends onto the dorsomedial surface of the frontal and
parietal cortex, so-called "watershed areas".(watershed = supplied by two arteries, at the borders of
their distribution)
middle cerebral artery

travels in the lateral sulcus; supplies insular cortex and lateral cortical surface.

The basilar artery is the other major source of arterial blood to !! PERFORATING
the cerebral cortex. In the region of the midbrain the paired ARTERIES !!
posterior cerebral arteries arise from the basilar artery. from the ant. and mid. cerebral
They supply the midbrain, contribute to the supply of the arteries supply the
hypothalamus and thalamus and then supply medial and basal forebrain
inferior surfaces of occipital and temporal lobes. - hypothalmus
VEINOUS DRAINAGE: - thalamus
The veins are named according to their location, superficial or deep to the cortical
mantle. - internal capsule
Superior superficial veins - basal ganglia
- drain the cortical surface
- empty into the superior or inferior sagittal sinuses.
Inferior superficial veins
- empty into the cavernous and transverse sinuses.
Deep cerebral veins include the internal cerebral veins which drain much of the thalamus and striatum and then pass through the
transverse cerebral fissure to unite and form the great cerebral vein (of Galen), which empties into the straight sinus.
STROKE syndromes: where is the clot??
MCA: If the entire MCA is occluded at its origin… Ant. Choroidal: supplies post. limb of internal
- contralateral hemiplegia, capsule
- hemianaesthesia, - contralateral hemiplegia,
- homonymous hemianopia, - hemianesthesia (hypesthesia),
- and a day or two of gaze preference to the - and homonymous hemianopia.
ipsi side
DOMINANT:
PCA: infarction of the medial temporal and occipital
- global aphasia, lobes.
- Dysarthria - Contra homonymous hemianopia with macula sparing
NON-DOMINANT: - Only the upper quadrant of vis. Field may be involved.
- anosognosia, - If the 2ndary visual association areas are spared and
- constructional apraxia, only the primary cortex is involved, the patient may be
aware of visual defects.
- and neglect are found - Acute disturbance in memory, particularly if dominant
ACA: usually well tolerated due to good collateral hemisphere involved. The defect usually clears
circulation. because memory has bilateral representation.
- Profound abulia (a delay in verbal and motor - If the dominant splenium of the corpus callosum is
response) involved, you alexia without agraphia.
- bilateral pyramidal signs with paraparesis - Visual agnosia for faces, objects, mathematical
symbols, and colors
- urinary incontinence - anomia with paraphasic errors (amnestic aphasia)
- Dyspraxia of left limbs,
- tactile aphasia in left limbs - peduncular hallucinosis (visual hallucinations of
brightly colored scenes and objects).
Arterial territories and Border zones (“watersheds”)
Cortical localisation

Language skills are represented in the left hemisphere in 95% of right handers and 70% of left-handers.
In the remaining cases, it is located either in the right hemisphere or bilaterally.
Early infancy left-hemisphere lesion = some or all language functions may develop in the right hemisphere.

Within the speech-dominant hemisphere:

Broca's area in the posterior, inferior region of the frontal lobe and
Wernicke's area, at the posterior end of the lateral sulcus are the primary language regions.
"expressive" or "Broca's" aphasia
impaired speech output and relative preservation of comprehension
"receptive" or "Wernicke's" aphasia.
speech output is fluent but nonsensical, and comprehension is
impaired
A "conduction aphasia" is characterised in patients by selective impairment in repetition tasks and results
when there is a disconnection between receptive and expressive speech areas.
In "transcortical aphasia", repetition is intact but other speech functions are impaired. Extensive crescent shaped
infarcts in the borderzones ("watershed areas") between major cerebral arteries may cause transcortical aphasia.
Mutism or abulia may occur if there is damage to the medial frontal/ cingulate cortical regions.
Gerstmann Syndrome =
- left/right disorientation, These deficits indicate dysfunction in tertiary association cortex in the dominant parietal
- dysgraphia, lobe. However, (i) these defecits rarely occur in isolation after left parietal damage (ie.,
- finger agnosia impairments in language dysphasia, reading dyslexia and coordinated motor skills
dyspraxia are also common and (ii) their presence does not indicate that dysfunction is
- dyscalculia. limited to the left parietal lobe.

The non-dominant hemisphere is somewhat more important for visuospatial skills.

Lesions in the non-dominant parietal region may cause disorientation or neglect which is characterised by
inattention to the contralateral side of the body and/or space.
Clock drawing is sometimes used as a bedside assessment tool to look for evidence of visuospatial
dysfunction.

The representation of musical skills appears to involve both cerebral hemispheres.

 Function of the cerebral cortex
primary sensory areas
CONTRLATERAL BODY receptors
transmit to
THALAMUS
transmits to PRIMARY SENSORY AREAS
TOPOGRAPHICAL: body areas represented in discrete areas of the cortex,
eg. somatosensory homunculus
! Blood supply to upper body sensorymotor band
IS DIFFERENT from blood supply to lower body;
THUS stroke may affect one and not the other !!

REGIONS WITH GREATER INPUT

ARE OVER-REPRESENTED

wernicke
Broca

PRIMARY
- Inputs from a specific
part of the THALAMUS
- TOPOGRAPHICAL
conections
FUNCTION is to
RECEIVE and PASS ON
Areas:
Somatosensory
= postcentral gyrus
Visual
= on the banks of the
calcarine sulcus
= surrounded in secondary
processing areas
Auditory
= small area at the
transverse gyrus of Heschl
(on sup. temporal lobe;
buried in lateral sulcus)
Gustatory
=insula and opercula of the (colour, orientation, motion)
temporal lobe
Motor
= Precentral gyrus
= executive function; no real Wernicke’s area
control of fine movements
SECONDARY
- For each primary
area there is a set
of secondaries
- THUS:
INPUTS mainly from cortex
FUNCTION is to
PROCESS,
ADD DETAIL,
COMPARE TO MEMORY
Areas:
Somatosensory @ opercula
Visual @ occipital lobe
Auditory @
Plenum temporale, under
Motor @ caudal frontal lobe
= the organgrinder; orders the
primary motor area to make
specific movements.
memory
LANGUAGE
Lesion = “aphasia”
HIGHER ORDER
BROCA AREA
Inputs from many
=inf frontal gyrus
areas are integrated
= Motor for speech
here
PREFRONTAL: = expressive area
The ASSHOLE centre: LESION:
Social and moral reasoning telegraphic speech;
Personality, thinking,
cognition; poor grammar
MOVEMENT: determines the (but conscious of
most appropriate trajectories mistakes)
of motion
SHORT TERM MEMORY
PARIETAL: WERNICKE AREA
Usually Rt. Lobe dominant = sup temporal gyrus,
Attention; focus, recognition
= inf parietal lobe
Filters relevant from
irrelevant sensory/receptive speech
CINGULATE: LESION:
Anxiety; autonomic Nonsensical speech, no
control, eg. drooling relevance to question
INSULA: asked but fluent
Love; pain
(palaeospinothalamic tract)
ORBITOFONTAL: CONDUCTION
Morality, self-evaluation,
Right-and-wrong decisions
TEMPORAL:
Fear, sexual function
Structure of the cerebral cortex
Meaningless Statistics: Cortex = about 250 000mm 2 in area; contains about 10 9 neurones
Anatomy:divided into 4 lobes that reflect the overlying bones of the skull: frontal, occipital, parietal, temporal.
HISTOLOGY:
2 major classes of neurons: PYRAMIDAL and STELLATE (granular):
Pyramidal = organise the stratification of processing, reach between layers, extend axons out of cortex
Stellate = interneurons, excitatory OR inhibitory function- but local
Brainstem:
Influence via
disseminated
catecholaminergic Layer 1: poor in cells, only stellate neurones.
neuron endings all
over the cortex
IPSI
Layer 2:
smallish stellate and pyramidal cells:
CORTEX THIS IS WHERE INTELLIGENCE HAPPENS

Layer 3:
THALAMUS Normal stellate and pyramidal cells;
The axons of this layer go to contralateral cortex
THUS: make up MOST OF CORPUS CALLOSUM
(it is said they PROJECT CALLOSALLY)

CONTRA Layer 4: Thalamic Lamina, only stellate

CORTEX
Layer 5:
GIANT pyramidal cells,
projecting to all subcortex
eg. to Cranial nerve nuclei (Corticobulbar tract)
subcortex - Muscles via spinal cord (corticospinal tract)

Layer 6:
- Project back to thalamus

Two major classes of neurones are present:

pyramidal cells and nonpyramical (which include stellate) cells; + supporting glial cells
Pyramidal cells are characterised by
- triangular shape to the cell body
- an axon that projects away from the cell's location
- two sets of dendrites.
- Apical dendrite projects vertically towards the
cortical surface,
- basal dendrites ramify below the cell body.

Nonpyramidal cells are smaller and more diverse,

many which do not have a projecting axon serve as
interneurones.
They may be excitatory or imhibitory to their neighbours and
serve to modulate the local transmission of information.
CENTRAL PAIN PATHWAYS
All primary afferent neurons are PSEUDOUNIPOLAR
i.e they sit in the periphery and send fibres towards the CNS.

Both spine and spinal trigeminal nucleus are arranged into concentric LAMINAE
10 laminae in total; numbered post to ant
LAMINA 10 = around central canal.
Lamina 1 = most posterior;
Laminae 8 and 9 = most anterior
** LAMINA 8 =Responsible for REFLEXIVE WITHDRAWAL; full of interneurones**

IN THE SPINE: After the laminae:

Fibres cross the midline @ level of entry;
form CONTRALATERAL FIBRE BUNDLE “Anterolateral tract”
Which consists of
SPINOTHALAMIC tract
synapses in
THALAMUS;
SPINORETICULAR tract
synapses in
ventrolateral medulla
(cardiorespiratory control)
+ Solitary tract nucleus
SPINOMESENCEPHALIC tract
synapses in
pons/midbrain,
periaqueductal gray
THUS: links emotion to
pain,
some autonomic control

IN THE TRIGEMINAL NUCLEUS: After the laminae:

The fibres ALSO CROSS OVER into contralateral side
Follow roughly same path as the anterolateral tract of the spinal
column

MAKE THE SAME CONNECTIONS with

THALAMUS, VENTROLATERAL MEDULLA,
PERIAQUEDUCTAL GRAY
@ Thalamus, there is a massive termination of fibres
– carrying information about noxious events across the entire body
IN THE THALAMUS:
VENTROPOSTERIOR THALAMUS
Also:
medial and intralaminar group of thalamic
nuclei
which are intimately connected
with cingulate cortex, medial prefrontal
cortex
= critical for the elaboration of emotional
responses and in modifying motivational states.

VENTROPOSTERIOR NUCLEI

Organised into topographical regions:

- there is a point for point

representation of body
areas
From there, signals are relayed
to somatosensory (postcentral gyrus)
THUS: pain sensation is integrated
with normal tactile sensation

Neurobiology of Pain
the consequences of pain present in two global categories,
"activating"
- evoking fight or flight, EXAMPLE: Cutaneous pain
- hypertension,
- tachycardia
- general arousal;
"deactivating"
- evoking quiescence, EXAMPLE: Deep chronic visceral pain
- loss of interest in the environment
- hypotension
- bradycardia
- sometimes nausea and fainting.

THERE ARE 2 SYSTEMS FOR INTEGRATING RESPONSES TO PAIN:

THESE SYSTEMS ARE ACTIVATED BY DISTINCT TYPES OF PAINFUL EVENTS.

Projections to the medulla (spino- and trigemino-reticular tracts)

almost certainly play a critical role in producing the changes in autonomic
activity associated with certain types of pain; eg. crying,
Projections to the midbrain (spino- and trigemino-mesencephalic tracts)
likely play critical roles in integrating the somatic and behavioural
responses to pain from different regions or following distinct timecourses.
Projection of "pain pathways"to thalamic regions (spino- and trigemino-thalamic tracts)
other than the ventroposterior nuclei (VPl and VPm): THERE ARE ALTERNATIVE PATHWAYS
Eg. Mediodorsal thalamus to frontal cortex:
these may mediate pain-associated depression
THUS: pain = motivational state like hunger and thirst,
NOT SENSORY DOMAIN LIKE VISION
LATERAL ANATOMY OF THE BRAIN: in unnecessary detail
MEDIAL ANATOMY OF THE BRAIN: in unnecessary detail
INFERIOR ANATOMY OF THE BRAIN: in unnecessary detail
Mechanism of Headache: Pain Pathway
“Primary” (idiopathic) headache: Migraine and Tension headache = most common
“Secondary” headaches are associated with intracranial pathology
eg. space-occupying lesions, increased ICP, stroke, hemorrhage, etc.

PAIN-SENSITIVE SCALP AND INTRACRANIAL STRUCTURES:

- proximal parts of cerebral and dural arteries,
- scalp arteries,
- the large veins and venous sinuses,
- scalp and other extracranial muscle (particularly in tension-type headache)
MOST IMPORTANT SENSORY NERVES: Trigeminal and C1
C3 (referring to occipital and neck areas)
DISTORTING
STIMULUS: Stretch DRUGS:
- Vasodilation Receptors - NSAIDS block COX1 and COX2
- Stretching - activity
- Local Inflammation - PARACETAMOL
- AMITRIPTILINE
Afferent trigeminal
SWOLLEN, pain fibres
PULSATILE
qualities of A mnemonic for the branches of the
headache TRIGEMINAL NERVE:
conveyed by the Trigeminal ganglion
blood vessels: Two Zulus Buggered My Cat.
PAIN MAY BE Temporal, Zygomatic, Buccal,
ALLEVIATED
Mandibular, Cervical.
compressing
extracranial
vessels, thus SPINAL
reducing blood TRIGEMINAL
flow and vessel NUCLEUS THALAMUS and then
stretching: Signal transduced and Cross to HIGHER CORTICAL
transmitted contralateral CENTRES
SO RUB * Reflex arcs work here
THOSE
- The ROOT of migraine:
TEMPLES!
Inept system of intracranial blood flow
regulation which allows such stresses to
befall the poor intracranial vessels
MIGRAINE WITH AURA: 30% of cases
Aura symptoms:
- nausea
- photophobia
- PHONOphobia
- “premonitary” sensations, eg. zigzag patterns in field of vision
AURA = result of MOVING CHANGES due to REDUCED CEREBRAL BLOOD FLOW
Due to misregulation of ARTERIOLAR BLOOD FLOW
= Is termed OLIGAEMIA, “spreading hypoperfusion”
Typically starts @ PRIMARY VISUAL CORTEX
2-3 minutes later it progresses to other, larger areas
HEADACHE PHASE begins soon.
The headache phase is characterised by extra- and intra-cranial arterial DILATION
MIGRAINE WITH AURA: 30% of cases
= NO MEASURABLE CHANGES TO CEREBRAL BLOOD FLOW, initially;
@ HEADACHE PHASE, the arteries still dilate
Pain Pathways in General
INFLAMMATION: TISSUE DAMAGE
Release of Accompanied by
- Bradykinin mechanical,
- Histamine chemical or
temperature change
- Serotonin

Noxious Release of K+
stimulus Directly stimulates
Eg. pressure, nociceptors
temperature etc

SENSITISATION NOCICEPTORS
of nociceptors ACTIVATED

Release of
SUBSTANCE P

NEUROPATHY A-Delta Fibres: C-Polymodal Fibres:

Mediated by A-δ fibres - FAST - SLOW
- At RECEPTOR LEVEL: - “FAITHFUL” - PROMISCUOUS
Spontaneous nociceptor activity (eg. small - MYELINATED - UNMYELINATED
neuroma growing like a cap at the end of the - Group III Fibres - Group IV fibres
noci axon. - ACUTE + SOMATIC PAIN DULL + VISCERAL PAIN
… or, spontaneous activity of the 2ndary neuron
which loses all stimulus, becomes unstable and
depolarises for no reason other than boredom DORSAL ROOT GANGLION
- At DRG + FIBRE LEVEL:
Sympathetic Sprouting where sympathetic 2ndary Neurons at
efferents travelling together with severed Lamina I and II of the
nociception fibres sprout abnormal links and DORSAL HORN
begin to stimulate the alpha-2 adrenoceptors on
the noci fibre, thus causing pain stimulus as an
effect of normal autonomic efferent signalling

- At SYNAPSE LEVEL: Neospinothalamic tract Palaeospinothalamic tract

Sensitisation of 2ndary neurons by
upregulation of glutamate NMDA receptors, … plus some pain fibres travel up the DCT
which are those most important for pain
transmission
Spinothalamic
DECUSSATION =
- At DORSAL HORN LEVEL: At the level of
Sprouting of new connections into the laminae the spinal cord
1 and 2 (pain) from laminae 3, 4 and 5 (touch)

THUS light touch and temperature become
misrepresented as pain BRAINSTEM
-Or: Loss of Local Inhibition through spinal RETICULAR
interneuron “gating” which normally limits the FORMATION
amount of signals transmitted to higher CNS
Or: Loss of Central Inhibition in the higher
CNS which directs afferent gating of pain stimuli;

THALAMUS

The cell bodies of all primary sensory neurons are found

within ganglia, and nociceptors are no exception.
body = cell bodies in dorsal root ganglia;
orofacial region and dura = trigeminal (Gasserian) ganglia SOMATOSENSORY
CORTEX
BRAIN TUMORS
INCIDENCE:
about 15 in 100,000
ONLY KNOWN RISK FACTOR is cranial irradiation
Proposed risk factors include mobile phone radiation, high tension wires and head trauma
Clinical presentation of brain tumours
Usually the result of increased intracranial pressure: Normally 0 to 15 mm Hg; over 30 requires treatment
th
- 6ths and 4 cranial nerve problems
- diffuse headache, worse in the morning
- PAIN CAN BE THROBBING AND UNILATERAL, LIKE A MIGRAINE!! BEWARE !!
TYPICAL PRESENTATION:
- Focal symptoms (eg. dysphasia, hemiparesis)
- Rate of progression = indication of degree of malignancy
- Usually: SUBACUTE ONSET, months to weeks
- Seizures are present in 15 to 95% of tumours (depending on subtype)

DEATH FROM A BRAIN TUMOUR is usually due to TONSILLAR HERNEATION from increased ICP
Thus, coma and death from respiratory failure
Diagnosis of a Brain Tumour
MRI is gold standard; no MRI findings = no lesion.
-
- Contrast agents get through broken blood-brain barrier
- CT can MISS some tumours!
- PET can distinguish high- from low-grade
PROGNOSIS OF A BRAIN TUMOUR
- Tumour Grade is ALL-IMPORTANT! Single most valuable prognostic factor
- Age (younger = better)
- Clinical status (i.e comorbidities, etc)
- THESE influence the outcome MORE THAN TREATMENT
Types of brain tumours
GLIAL: oligodendroma and astrocytoma
ASTROCYTOMA:
- A terrible beast which spreadeth yonder aong the white matter tracts, thus
rendering itself INOPERABLE
- Young adults most stricken
- First symptom OFTEN A SEIZURE
- Looks like a non-enhancing mass on MRI
- PET will show high-activity regions: try to biopsy THESE
(normally, biopsies are not representative as different regions will have different histology, so
you want to hit the most active high-grade areas with the biopsy needle)
- These tumours will eventually become high grade.
SURVIVAL about 5 years
- TREATED WITH RESECTION (when you can) and RADIATION

ASTROCYTOMA FROM HELL: GLIOBLASTOMA MULTIFORME

- Commonest and worst
- 50-70 age group
- irregular ring-like lesion on MRI findings; +edema and mass effect
- necrotic, with pseudopalisading of cells; lots of vascular proliferation
SURVIVAL about 1 year.
- p53 and epidermal growth factor receptor mutations are the culprit here.
- TREATED with radiotherapy and surgery whenever possible

OLIGODENDROMA: given a choice, this is the tumour you would want.

- 20% of glial tumours
- looks like an astrocytoma on MRI
- “fried-egg” appearance under the microscope
- delicately vascular, prone to hemorrhage
- THE ONLY BRAIN TUMOUR THAT CALCIFIES!
Thus, you might actually see it on a plain skull X-ray (!)
SURVIVAL: usually about 16 years; most eventually progress in malignancy
TREATED with chemo radio and surgically.
 MENINGIOMA
- Arises from arachnoid cells
- About 20% of all brain tumours
- Majority are asymptomatic and are found en route to another diagnosis
- Whorls of cells on microscopy: identical to normal arachnoid cells
- Slowly growing
- Genetic abnormality: absence of chromosome 22
- WHEN OVER HEMISPHERES it produces hemiparesis and seizures
- In the base of skull, it will cause cranial nerve palsies
- MRI shows a tethered tumour with a “dural tail”
- Treated with resection only. 20% will recur in 10 years.
SCHWANNOMA
- Peripheral nerve sheath cells gone bad: most often sensory nerves
- 10% of brain and 30% of spine tumours
- Angle of cerebellum and pons is a favourite:
here, they are called ACOUSTIC NEUROMA

Functional Brain Imaging:

MRI takes a semester to explain. Here is a popular science view:
- Based on the laws of electromagnetism, any electrically charged particle which moves
creates a magnetic field called a magnetic moment
- This makes every hydrogen atom in the body a tiny magnet with a north and south pole (a
magnetic dipole)
- Each hydrogen atom is also spinning along its own little axis (thus it is a moving charge)
- These axises (axes?) are normally all facing different directions.
- Now, you put these atoms into a magnetic field, and they all line up parallel to the field
(or face the opposite direction. The point is- they line up.)

- NOW: these atoms, though facing in generally the same direction, DON’T ACTUALLY
ALIGN PRECISELY. Their axis wobbles in a cone-shaped trajectory. Essentially, this is
what happens when a spinning top starts slowing down.
- This wobble is called precession
- The speed of wobbling is called the precessional frequency
- NOW you get a large radiofrequency gun, and aim it at exactly 90 degrees (perpendicular)
to the direction of the magnetic field which has aligned them. The hydrogen atoms must
get hit IN THE SIDE by the RF pulse.

- Getting hit with this radiofrequency photon misalignes the hydrogen atoms. They
literally flip, either 90 (perpendicular, facing the direction in which the RF pulse was
travelling) or 180 degrees (i.e they reverse direction)
- BUT they are still in a magnetic field, and thus they will try to realign themselves.
- THEY DON’T ALL COME BACK AT ONCE; it takes a little while to return to the normal
parallel alignment.
- As they slowly rotate back to face the big magnet, they become less perpendicular and
more parallel.
- The return to parallel is called longitudinal relaxation , or T1 recovery
- The deviation from the perpendicular is called transverse relaxation, or T2 decay
Thus, T1 recovery is gradually increasing after a pulse, and T2 decay is, well, decaying.
The transverse magnetization induces a voltage in an antenna or receiver coil which will
be eventually become the MR signal
T1 recovery occurs because of the influence of the big magnetic field
T2 decay occurs because of neighbouring hydrogen atoms interacting with each other.
- THUS: T1 time tells us about how molecularly mobile or “glued-down” the
hydrogen atoms are; i.e fat hydrogen is less mobile than water hydrogen
- T2 tells us how many hydrogen atoms are near each other (i.e the greater their
density, the faster they interact and the faster does the T2 signal fade)
More painful detail at http://www.erads.com/mrimod.htm