Lecture 1 Flashcards
1
Q
Headache and its associated features are the disorder itself
A
primary
2
Q
Cause by an exogenous disorder (additional clinical features and pathology beyond the headache)
A
secondary
3
Q
What is the most common cause of primary headache?
A
tension-type
4
Q
What are the most common types of secondary headaches?
A
systemic infection
5
Q
What are the common types of primary headaches?
A
6
Q
What are the common types of secondary headaches?
A
7
Q
What is the epidemiology of migraines?
A
- Second most common cause of primary headache
- affects 15% of women and 6% of men over a one year period
8
Q
Benign recurring headache that is associated with particular additional neurologic signs and symptoms (typically accompanies by nausea, vomiting, associated w/ triggers)
A
migraine
9
Q
What is the key pathway for pain in migraines?
A
Trigeminovascular input
10
Q
Describe the pathway of pain in migraines?
A
from the meningeal vessels –> trigeminal ganglion –> synapses on second-order neurons in the trigeminocervical complex (TCC) in the brainstem –> thalamus –> cortex
11
Q
Important modulation of the __ __ input comes from midbrain nuclei in migraines
A
trigeminovascular nociceptive (pain)
12
Q
What seems to be the cause of pain in migraines?
A
Problems with modulation of pain sensation from trigeminal afferents (dorsal raphe nucleus, locus coeruleus, and nucleus raphe magnus) seems to be the cause
- Abnormal pain sensation related to vascular dilation and constriction
13
Q
Where are 5-HT1 receptors important in?
A
trigeminal nucleus & thalamus
14
Q
What do 5-HT1 receptors bind to?
A
serotonin
15
Q
Which class of drugs block the 5-HT1 receptors?
A
-triptans (i.e., sumatriptan) - used acutely early on
16
Q
What receptor is important in migraines?
A
5-HT1
17
Q
What neurotransmitter is important to migraines?
A
CGRP (calcitonin-gene-related peptide)
18
Q
Where is CGRP (calcitonin-gene-related peptide) active at?
A
- trigeminal ganglion
- vasoactive efferents
19
Q
What is the function of vasoactive efferents ?
A
a vasodilator and seems to increase pain sensation when it is released at the trigeminal ganglion & vasoactive efferents
20
Q
__ __ that bind and eliminate CGRP (thus preventing it from binding to its receptor) are effective for headache prevention
A
Monoclonal antibodies
21
Q
What is the best accepted theory of migraines?
A
primary neural dysfunction (neurovascular)
22
Q
What is primary neural dysfunction?
A
wave of “spreading depression” (slowly travelling wave of neural excitability) travels through the cortex and leads to activation of the trigeminal complex
23
Q
What type of pain does wave of primary neural dysfunction lead to?
A
vascular-generated pain
24
Q
What is the ‘spreading’ depression wave though to be linked to?
A
- visual changes, other aura findings
- modulation of nociceptor afferents by locus ceruleus and dorsal raphe nucleus
25
What is the 'spreading depression' called 'depression'?
because after the excitatory wave spreads, that area is often refractory to synaptic excitation or action potentials
26
What is the etiology of migraines?
- strong genetic component, but no clear candidate genes for most causes
- 70% have a 1st degree relative with migraine
- Difficulty identifying the genes, though – perhaps VG calcium channels
27
Signs and symptoms of migraines?
28
What are symptoms that typically precede the migraines & aura (aka prodrome)?
- can include: sensitivity to light, sound, odors
- Lethargy, fatigue or constant yawning
- food cravings, thirst, polyuria or anorexia
- constipation or diarrhea
- Neck discomfort
- Mood changes, brain fog
29
What does symptoms of the aura of a migraine?
- visual field deficits
- tunnel vision
- scotoma – an area of impaired vision with a flashing light border
- paresthesias
- heaviness of limbs
- confusion, speech/language difficulties
30
What is an aura?
symptoms that can occur before or during a migraine (55% have no aura)
31
What is diagnostic criteria for migraines?
Repeated attacks of headache lasting 4 - 72 h in patients with a normal physical examination, no other reasonable cause for the headache, and:
- At least 2 of the following: unilateral pain, throbbing pain, aggravation by movement, moderate or severe intensity
- Plus at least one of the following: photophobia & phonophobia, nausea and/or vomiting
32
What are the attributes of the POUND screen for migraines?
- Pulsatile quality?
- Headache for 4 – 72 hours?
- Unilateral?
- Nausea and Vomiting?
- Severe intensity?
If >= 4 then migraine is likely (+LR = 24)
33
What are the 4 types of migraines?
- Acephalgic migraine
- Common migraine
- Classic migraine
- Complicated migraine
34
Define an acephalgic migraine?
- Migraine without headache, just the aura and the prodrome
- 1/3 of patients referred for vertigo or dizziness
35
Define a common migraine.
migraine without aura
36
Define a classic migraine.
migraine with an aura
- headache typically follows aura after no more than 60 minutes
37
Define a complicated migraine.
has severe or persistent (reversible) sensorimotor deficits
- i.e. diplopia, severe vertigo, ataxia, altered level of consciousness
- Hemiplegia, loss of vision
38
Define tension-type headache.
chronic head-pain syndrome characterized by bilateral tight, bandlike discomfort
- pain typically builds slowly, fluctuates in severity, and may persist more or less continuously for many days
- headache may be episodic or chronic (present >15 days per month)
39
Why is a tension-type headache not a migraine?
Lack nausea, vomiting, photophobia, phonophobia, osmophobia, throbbing, and aggravation with movement but one or a couple of these may be present to a minor degree and still be a TH
40
What is the pathophysiology of a tension headache?
- increased muscle tension
- likely due to increase sensitivity to myofascial pain (chronic forms may be due to dysregulation of pain sensation in the central nervous system)
- No clear pathophysiology yet
41
What are symptoms of a tension headache?
- Pressing or tightening (nonpulsatile quality)
- Frontal-occipital location
- Bilateral - Mild/moderate intensity
- Not aggravated by physical activity (though physical activity during a tension headache isn’t really fun, doesn’t significantly make the headache that much worse)
42
What are the diagnostic criteria for tension-type headaches?
- At least 10 previous headaches
- Duration of 30 minutes to 7 days
2 of the following characteristics must be present:
- Pressing or tightening (non-pulsating) quality
- Mild-moderate in severity (inhibits but does not prevent activity)
- Bilateral
- Not aggravated by routine activity
- No nausea or vomiting
- Photophobia or phonophobia may be present, but not both
43
A group of headache syndromes is known as trigeminal autonomic cephalalgias (TACs) , what does this include?
- cluster headache
- paroxysmal hemicrania
- SUNCT (short-lasting unilateral neuralgia-form headaches with conjunctival injection and tearing)
- SUNA (like above but with any autonomic symptoms)
44
Which headache do most describe as excruciating?
trigeminal autonomic cephalalgias (TACs)
45
What is the pathogenesis of trigeminal autonomic cephalalgias (TACs)?
- might be linked to hypothalamic/circadian circuits
- vasodilation thought to be a result, not a cause, of underlying CNS dysregulation
- vasodilation may be responsible for the autonomic nervous system findings, though (dilation of carotid artery may compress sympathetic fibres, resulting in a “shift” towards parasympathetic activation)
46
Compare and contrast cluster headaches, paroxysmal hemicrania, and SUNCT. (gender, type, severity, site, frequency, duration of attack, autonomic features)
47
What are features of a cluster headache?
- Episodic – tend to occur frequently (daily) for a period (weeks/months) and then there is a significant headache-free period
- tend to move about during attacks, pacing, rocking, or rubbing their head for relief; some may even become aggressive during attacks
- Autonomic symptoms are unilateral
48
What is the diagnostic criteria for cluster headaches?
49
What are many secondary headaches associated with?
elevations in intracranial pressure or irritation of the meninges
50
What are structures that sense pain in the CNS and can cause headaches?
- Intracranial vessels, dura mater are innervated by CN V
- Meningeal arteries, dural sinuses, falx cerebri, pial arteries
51
T/F: The scalp is not sensitive in secondary headaches
False, it is
52
What is the criteria for low-risk headaches?
- Age younger than 30
- Features typical of primary headache
- Previous history of similar headaches
- No abnormal neurologic findings
- No concerning change in the usual headache pattern
- No “red flag” findings in the history or physical exam
- To discuss later as we address more neuropathology
- No serious medical conditions that could have a secondary serious headache as a complication
(i.e. history of brain tumour, HIV)
53
What are disorders involving elevated intracranial pressure?
- Normal Pressure Hydrocephalus
- Idiopathic Intracranial Hypertension
- edema
54
What are the 3 major types of cerebral edema?
- vasogenic
- cytotoxic
- interstitial edema
55
Describe a vasogenic cerebral edema?
- blood-brain barrier disruption and increased vascular permeability
- fluid shifts from the intravascular compartment to the intercellular spaces of the brain
- little to no lymphatics, therefore difficult to remove this excess fluid
- localized (e.g., adjacent to inflammation or neoplasms) or generalized (generalized can be due to uncontrolled hypertension / local can be due to infection, cancer)
56
Describe cytotoxic cerebral edema.
- increase in intracellular fluid secondary to neuronal, glial, or endothelial cell membrane injury
- i.e. from generalized hypoxic/ischemic insult or with metabolic damage – any cause of cell death
57
Describe interstitial edema.
- usually occurs around the lateral ventricles
- increased intraventricular pressure causes an abnormal flow of fluid from the intraventricular CSF across the ependymal lining to the periventricular white matter
- mostly due to hydrocephalus, increased intracranial pressure
58
What are consequences of cerebral edema?
- gyri flatten
- sulci narrow
- ventricular cavities are compressed / Or they can expand if the cause of edema is interstitial due to hydrocephalus
- As brain expands, herniation may occur
- signs and symptoms of increased intracranial pressure
59
What is hydrocephalus?
accumulation of excessive CSF within the ventricular system
60
Why does hydrocephalus occur?
- most cases occur as a consequence of impaired flow and resorption of CSF
- rarely overproduction of CSF causes hydrocephalus (tumours of the choroid plexus)
61
What does hydrocephalus look like in a young individual before closure of cranial sutures?
- enlargement of the head (increase in head circumference = macrocephaly)
62
What does hydrocephalus look like in an older individual after closure of cranial sutures?
- enlargement of the ventricles and increased intracranial pressure
- can result in atrophy/compression of the surrounding brain tissue
63
What is communicating hydrocephalus?
- enlargement of the entire ventricular system
- The fluid (and increased pressure) can “communicate” with each ventricle the major foramina must not be blocked
- More likely to be due to a fluid-producing mass
64
What is non-communicating hydrocephalus?
- only a portion of the ventricular system is enlarged
- example is a mass in the third ventricle, with back-up of fluid in the lateral ventricles but normal volumes in the fourth ventricle
- Blockage of the cerebral aqueduct
65
What are symptoms of raised intracranial pressure?
- Slowing of mental capacity
- headaches (especially if more severe in the morning) - Headache is rare in NPH
- vomiting (more likely in the morning)
- blurred and/or double vision - blurred = optic nerve atrophy due to papilledema, double vision = 6th cranial nerve palsy (usually)
- In kids – precocious puberty, stunted growth due to hypothalamic impairment
- Difficulty walking (spasticity)
66
What is a common type of hydrocephalus that becomes more common with age above 60?
normal pressure hydrocephalus
67
What is the pathogenesis of hydrocephalus?
- ventricular volume is increased, but subarachnoid volume is not
- cause is not well understood – impaired absorption at the arachnoid granulations?
- although pressures on lumbar puncture are fairly normal, ventricular enlargement and intracranial pressure is increased
- can also be caused by tumours, infections, subarachnoid hemorrhage
68
What type of hydrocephalus causes ventricular volume to increase but subarachnoid volume to not?
normal pressyre hydrocephalus
69
What are clinical features of normal pressure hydrocephalus?
- gradual progressive gait apraxia (“magnetic feet”), urinary incontinence, dementia are the typical triad
- bradyphrenia – slowness of thought, speech is another common finding
70
What is the treatment and prognosis of hydrocephalus?
improvement after a shunt is placed into the peritoneum
71
What type of disorder is of unknown etiology but predominantly affects obese women of childbearing age?
Idiopathic intracranial hypertension
72
What is Idiopathic intracranial hypertension?
chronically elevated intracranial pressure (ICP) leading to papilledema, which may lead to progressive optic atrophy and blindness
73
What are other names for Idiopathic intracranial hypertension?
pseudotumor cerebri, benign intracranial hypertension (BIH)
74
What is the epidemiology of Idiopathic intracranial hypertension?
- incidence is 1 in 100,000 (not common, but possibility of seeing it in practice
- `8-20 X increased risk in obese women
75
What is the pathogenesis of idiopathic intracranial hypertension?
- not clearly identified, however it is thought that there are subtle problems with drainage from venous sinuses, especially the transverse sinus
- although venous outflow is normal in most, there is an increased rate of arterial inflow in most as well
- therefore rate of arterial inflow is subtly greater than rate of venous outflow, resulting in increased intracranial pressure
- Unsure of how obesity contributes to pathophysiology
76
What are signs and symptoms of idiopathic intracranial hypertension?
- typical headache of ICP
- diplopia
- tinnitus
- visual field defects (usually transient early on)
77
How can you diagnose idiopathic intracranial hypertension?
lumbar puncture to determine opening pressure
78
How do you treat idiopathic intracranial hypertension?
- acute emergency treatment for elevated ICP
- weight loss can result in resolution in up to 90% of patients
79
What is a subfalcine (cingulate) herniation?
unilateral or asymmetric expansion of a cerebral hemisphere that displaces the cingulate gyrus under the falx cerebri
- can lead to compression of branches of the anterior cerebral artery (vascular symptoms - weakness of contralateral leg / limibic symptoms - apathy, difficulty making decisions, indifference)
80
What is a transtentorial (uncinate, mesial temporal) herniation?
medial aspect of the temporal lobe is compressed against the free margin of the tentorium cerebelli
- can result in 3rd cranial nerve palsy
- compression of the contralateral cerebral peduncle (hemiparesis)
- hemorrhagic lesions in midbrain and pons (Duret hemorrhage)
- hydrocephalus due to obstruction of CSF flow
81
What is tonsilar herniation?
Significant displacement of the cerebellar tonsils through the foramen magnum
82
Which hernation can be acute and life-threatening, why?
tonsillar herniation
- it causes brainstem compression and compromises vital respiratory and cardiac centers in the medulla oblongata
83
What is chronic tonsillar herniation?
less severe repercussions
- Some congenital malformations of the contents of the posterior fossa can show tonsillar herniation, but with minimal clinical features
84
What occurs during acute neuronal injury?
- on H&E stains, neurons look “redder” than usual due to increased eosinophilia
- pyknosis (a type of nuclear condensation), eosinophilic cell body, cell shrinkage, disappearance of the nucleolus, loss of Nissl substance
85
What is acute neuronal injury found?
Typically found 12-24 hours after hypoxic/ischemic insult
86
What is the process called that occurs during subacute/chronic neuronal injury?
neuronal degeneration
87
What are examples of neuronal degeneration?
as ALS or Alzheimer disease
88
What happens during subacute/chronic neuronal injury?
Cell loss and reactive gliosis
- proliferation, hypertrophy of astrocytes - Hyperproliferative, hyperplastic astrocytes = gemistocytic astrocytes
- activation of microglial cells - Activated microglial cells also change their morphology - their processes also get “fatter” and shorter
- neuronal cell loss can be difficult to detect – although neurons from certain functional areas are lost, they’re not usually lost “all at once” - Easier to see the gliosis than the cell loss
89
What is cell loss often due to in subacute/chronic neuronal injury?
apoptosis
90
What is gliosis (reactive gliosis)?
- hypertrophy and hyperplasia of astrocytes
- nuclei enlarge and nucleoli become more prominent
- cytoplasm becomes more eosinophilic, processes more stout - Known as gemistocytic astrocytes
91
What are benefits of astrocytic gliosis?
- Help with synaptogenesis after injury? Controversial – likely more of a barrier than an aid in “reconnecting” the damaged brain
- important in buffering excitotoxins (glutamate), acid, potassium
- important in maintaining or re-establishing the BBB
- Improved ability to support neuron energy metabolism increased
92
What is the disadvantage of astrocytic gliosis?
Axons have great difficulty navigating across the glial scar, may be a major barrier preventing regeneration of axons/tracts
93
Which cells exhibit minimal changes when brain tissue is damaged?
Oligodendrocytes and ependymal cells
94
What are microglial changes that are seen when brain tissue is damaged?
microglial activation
cells lose their ramifications and become more “ameboid”
- secrete pro-inflammatory molecules and cytokines that recruit peripheral leukocytes and aid astroglial activation
- secrete free radicals that can add to neuronal injury
- phagocytose dead or dying cells
95
Intracellular inclusions are common w/ a range of neurolgical diseases such as?
- lipofuscin: accumulates with aging, “wear-and-tear” complex of lipids
- viral inclusions (Cowdry = intranuclear inclusion associated with herpes infection, Negri body = intracytoplasmic inclusion associated with rabies)
- Neurofibrillary tangles (Alzheimer disease)
- Lewy bodies in Parkinson disease
96
What are responses to ischemia in the CNS?
Excitatory amino acid neurotransmitters (glutamate) are released during ischemia & may cause cell damage by overstimulation and persistent opening of NMDA receptor – glutamate ionotropic receptors
- These receptors allow calcium influx
- Calcium influx can increase nitric oxide production in neuronal cells
97
Certain glutamate receptors, NMDA receptors in particular, are permeable to __.
calcium
98
Why might a cell depolarize with ATP depletion?
Less ATP to the cells --> ion pumps (ex., NA+/K+ pumps) become impaired --> influx of Na+ into the cell --> depolarization
99
How does increased intracellular calcium lead to increased nitric oxide production?
Increased intracellular calcium levels can stimulate the production of nitric oxide (NO) through the activation of an enzyme called nitric oxide synthase (NOS). Nitric oxide synthase catalyzes the conversion of the amino acid L-arginine into nitric oxide and citrulline
100
What happens in early insult (minutes-hours) of a stroke (ischemia)?
loss of intracellular ATP --> destabilization of membrane potentials, excitotoxicity, calcium influx and nitric oxide production --> destruction of membranes and necrosis
101
What happens during later insult (hours-day) of a stroke (ischemia)?
development of red neurons (dead, shrunken, eosinophilic, pyknotic cells)
- microglial activation, disruption of BBB at this time
102
What happens during subacute phase of insult (day-days) of a stroke (ischemia)?
reactive astrocytes, reactive microglia, influx of leukocytes across BBB – known as liquefactive necrosis
103
What is the resolution of ischemia (stroke)?
astrocytic “scar” develops, liquefied mass removed
- sometimes leaving a cavity bounded by scar
- Sometimes necrotic area is composed completely of gliotic tissue and new vascular elements (no neurons)
104
105
What is liquefactive necrosis characterized by?
digestion of the dead cells --> transformation of the tissue into a liquid viscous mass
106
For unknown reasons, hypoxic death of cells within the central nervous system often manifests as __ __
liquefactive necrosis
107
Where is liquefactive necrosis seen?
seen in focal bacterial or, occasionally, fungal infections --> accumulation of leukocytes --> purulent inflammation (pus)
