1

Stroke

Classification of Headache by the International Headache Society.

1. Migraine
1.1 Migraine without aura
1.2 Migraine with aura
1.2.1 Migraine with typical aura
1.2.2 Migraine with prolonged aura
1.2.3 Familial hemiplegic migraine
1.2.4 Basilar migraine
1.2.5 Migraine aura without headache
1.2.6 Migraine with acute onset aura
1.3 Ophthalmoplegic migraine
1.4 Retinal migraine
1.5 Childhood periodic syndromes that may be precursors to or
associated with migraine
1.5.1 Benign paroxysmal vertigo of childhood
1.5.2 Alternating hemiplegia of childhood
1.6 Complications of migraine
1.6.1 Status migrainous
1.6.2 Migrainous infarction
1.7 Migrainous disorder not fulfilling above criteria

2. Tension-type headaches
2.1 Episodic tension-type headache
2.1.1. Episodic tension-type headache associated with disorder of
pericranial muscles
2.1.2. Episodic tension-type headache unassociated with disorder
of pericranial muscles
2.2 Chronic tension-type headache
2.2.1. Chronic tension-type headache associated with disorder of
pericranial muscles
2.2.2. Chronic tension-type headache unassociated with disorder
of pericranial muscles
2.3 Headache of the tension-type not fulfilling above criteria.

3. Cluster headache and chronic paroxysmal hemicrania

3.1 Cluster Headache
3.1.1. Cluster headache periodicity undetermined
3.1.2. Episodic cluster headache
3.1.3. Chronic cluster headache
3.1.3.1. Unremitting from onset
3.1.3.2. Evolved from episodic
3.2 Chronic paroxysmal hemicrania
3.3 Cluster headache-like disorder not fulfilling above criteria

4. Miscellaneous headaches unassociated with structural lesion

4.1 Idiopathic stabbing headache
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4.2 External compression headache

4.3 Cold stimulus headache
4.3.1 External application of a cold stimulus
4.3.2 Ingestion of a cold stimulus
4.4 Benign cough headache
4.5 Benign exertional headache
4.6 Headache associated with sexual activity
4.6.1 Dull type
4.6.2 Explosive type
4.6.3 Postural type

5. Headache associated with head trauma

5.1 Acute post-traumatic headache
5.1.1 With significant head trauma and/or confirmatory signs
5.1.2 With minor head trauma and no confirmatory signs
5.2 Chronic post-traumatic headache
5.2.1 With significant head trauma and/or confirmatory
signs
5.2.2 With minor head trauma and no confirmatory signs

6. Headache associated with fascular disorders

6.1 Acute ischemic cerebrovascular disease
6.1.1 Transient ischemic attacks (TIA)
6.1.2 Thromboembolic stroke
6.2 Intracranial hematoma
6.2.1 Intracerebral hematoma
6.2.2 Subdural hematoma
6.2.3 Epidural hematoma
6.3 Subarachnoid hemorrhage
6.4 Unruptured vascular malformation
6.4.1 Arteriovenous malformation
6.4.2 Saccular aneurysm
6.5 Arteritis
6.5.1 Giant cell arteritis
6.5.2 Other systemic arteritides
6.5.3 Primary intracranial arteritis
6.6 Carotid or vertebral artery pain
6.6.1 Carotid or vertebral dissection
6.6.2 Carotidynia (idiopathic)
6.6.3 Post endarterectomy headache
6.7 Venous thrombosis
6.8 Arterial hypertension
6.8.1 Acute pressor response to exogenous agent
6.8.2 Pheochromocytoma
6.8.3 Malignant (accelerated) hypertension
6.8.4 Pre-eclampsia and eclampsia

6.9 Headache associated with other vascular disorder

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7. Headache associated with non-vascular intracranial disorder

7.1 High cerebrospinal fluid pressure
7.1.1 Benign intracranial hypertension
7.1.2 High pressure hydrocephalus
7.2 Low cerebrospinal fluid pressure
7.2.1 Post-lumbar puncture headache
7.2.2 Cerebrospinal fluid fistula headache
7.3 Intracranial infection
7.4 Intracranial sarcoidosis and other non-infectious inflammatory
diseases
7.5 Headache related to intrathecal injections
7.5.1 Direct effect
7.5.2 Due to chemical meningitis
7.6 Intracranial neoplasm
7.7 Headache associated with other intracranial disorder

8. Headache associated with substance or their withdrawal

8.1 Headache induced by acute substance use or exposure
8.1.1 Nitrate/nitrite induced headache
8.1.2 Minosodium glutamate induced headache
8.1.3 Carbon monoxide induced headache
8.1.4 Alcohol induced headache
8.1.5 Other substances
8.2 Headache induced by chronic substance use or exposure
8.2.1 Ergotamine induced headache
8.2.2 Analgesics abuse headache
8.2.3 Other substances
8.3. Headache from substance withdrawal (acute use)
8.3.1 Alcohol withdrawal headache (hangover)
8.3.2 Other substances
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8.4 Headache from substance withdrawal (chronic use)

8.4.1 Ergotamine withdrawal (chronic use)
8.4.2 Caffeine withdrawal headache
8.4.3 Narcotics abstinence headache
8.4.4 Other substances
8.5 Headache associated with substance but with uncertain mechanism

9. Headache associated with non-cephalic infection

9.1 Viral infection
9.1.1 Focal non-cephalic
9.1.2 Systemic

9.2 Bacterial infection

9.2.1 Focal non-cephalic
9.2.2 Systemic (septicemia)
9.3 Headaches related to other infection

10.Headache associated with metabolic disorder

10.1 Hypoxia
10.1.1 High altitude headache
10.1.2 Hypoxic headache
10.1.3 Sleep apnea headache
10.2 Hypercapnia
10.3 Mixed hypoxia and hypercapnia
10.4 Hypoglycemia
10.5 Dialysis
10.6 Headache related to other metabolic abnormality

11.Headache or facial pain associated with disorder of cranium,

neck, eyes, ears, nose, sinuses, teeth, mouth or other facial or
cranial structrures.
11.1 Cranial bone
11.2 Neck
11.2.1 Cervical spine
11.2.2 Retropharyngeal tendonitis
11.3 Eyes
11.3.1 Acute glaucoma
11.3.2 Refracative errors
11.3.3 Heterophoria or heterotropia
11.4 Ears
11.5 Nose and sinuses
11.5.1 Acute sinus headache
11.5.2 Other diseases of nose or sinuses
11.6 Teeth, jaws and related structures
11.7 Temporomandibular joint disease
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12.Cranial neuralgias, nerve trunk pain and deafferentation pain

12.1 Persistent (in contrast to tic-like) pain of cranial nerve origin
12.1.1Compression or distortion of cranial nerves and second or
third cervical roots
12.1.2Demyelination of cranial nerves
12.1.2.1 Optic neuritis (retrobulbar neuritis)
12.1.3Infarction of cranial nerves
12.1.3.1 Diabetic neuritis
12.1.4Inflammation of cranial nerves
12.1.4.1 Herpes zoster
12.1.4.2 Chronic post-herpetic neuralgia
12.1.5Tolosa-Hunt syndrome
12.1.6Neck-tongue syndrome
12.1.7Other causes of persistent pain of cranial nerve original
12.2 Trigeminal neuralgia
12.2.1Idiopathic trigeminal neuralgia
12.2.2Symptomatic trigeminal neuralgia
12.2.2.1 Compression of trigeminial root or ganglion
12.2.2.2 Central lesions
12.3 Glossopharyngeal neuralgia
12.3.1Idiopathic glossopharyngeal neuralgia
12.3.2Symptomatic glossopharyngeal neuralgia
12.4 Nervus intermedius neuralgia
12.5 Superior laryngeal neuralgia
12.6 Occipital neuralgia
12.7 Central causes of head and facial pain other than tic douloureux
12.7.1Anesthesia dolorosa
12.7.2Thalamic pain
12.8 Facial pain not fulfilling criteria in groups 11 or 12

3.Headache not classifiable

There are three major categories of headaches:

1. primary headaches,
2. secondary headaches, and
3. cranial neuralgias, facial pain, and other headaches

What are primary headaches?

Primary headaches include migraine, tension, and cluster headaches, as well as a

variety of other less common types of headache.

 Tension headaches are the most common type of primary headache. Up

to 90% of adults have had or will have tension headaches. Tension
headaches occur more commonly among women than men.
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 Migraine headaches are the second most common type of primary

headache. An estimated 28 million people in the United States (about
12% of the population) will experience a migraine headache. Migraine
headaches affect children as well as adults. Before puberty, boys and girls
are affected equally by migraine headaches, but after puberty, more
women than men are affected. It is estimated that 6% of men and up to
18% of women will experience a migraine headache in their lifetime.
 Cluster headaches are a rare type of primary headache affecting 0.1% of
the population (1 in a 1,000 people). It more commonly affects men in
their late 20s though women and children can also suffer these types of
headache.

Primary headaches can affect the quality of life. Some people have occasional
headaches that resolve quickly while others are debilitated. While these
headaches are not life-threatening, they may be associated with symptoms that
can mimic strokes or intracerebral bleeding.

What are secondary headaches?

Secondary headaches are those that are due to an underlying structural problem
in the head or neck. There are numerous causes of this type of headache ranging
from bleeding in the brain, tumor, or meningitis and encephalitis.

What are cranial neuralgias, facial pain, and other headaches?

Neuralgia means nerve pain (neur= nerve + algia=pain). Cranial neuralgia

describes a group of headaches that occur because the nerves in the head and
upper neck become inflamed and become the source of the pain in the head.
Facial pain and a variety of other causes for headache are included in this
category.

What causes tension headaches?

While tension headaches are the most frequently occurring type of headache,
their cause is not known. The most likely cause is contraction of the muscles that
cover the skull. When the muscles covering the skull are stressed, they may
spasm and cause pain. Common sites include the base of the skull where the
trapezius muscles of the neck inserts, the temple where muscles that move the
jaw are located, and the forehead.

There is little research to confirm the exact cause of tension headaches. Tension
headaches occur because of physical or emotional stress placed on the body.
These stressors can cause the muscles surrounding the skull to clench the teeth
and go into spasm. Physical stressors include difficult and prolonged manual
labor, or sitting at a desk or computer for long periods of time concentrating.
Emotional stress may also cause tension headaches by causing the muscles
surrounding the skull to contract.
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What are the symptoms of tension headaches?

The pain symptoms of a tension headache are:

 The pain begins in the back of the head and upper neck and is described
as a band-like tightness or pressure.
 Often is described as pressure encircling the head with the most intense
pressure over the eyebrows.
 The pain usually is mild (not disabling) and bilateral (affecting both sides
of the head).
 The pain is not associated with an aura (see below), nausea, vomiting, or
sensitivity to light and sound.
 The pain occurs sporadically (infrequently and without a pattern) but can
occur frequently and even daily in some people.
 The pain allows most people to function normally, despite the headache.

What causes cluster headaches?

The cause of cluster headaches is uncertain. It may be that certain parts of the
brain begin to malfunction for an unknown reason. The hypothalamus, an area
located at the base of the brain is responsible for the body's biologic clock and
may be the part of the brain that is the source for the headaches. When brain
scans are performed on patients who are in the midst of a cluster headache,
there is abnormal activity in the hypothalamus.

Cluster headaches also:

 tend to run in families and this suggests that there may be a genetic role;
 may be triggered by changes in sleep patterns;
 may be triggered by medications (for example, nitroglycerin, used for
heart disease).

If an individual is in a susceptible period for cluster headache, cigarette smoking,

alcohol, and some foods (for example, chocolate) also can be potential causes for
headache.

What are the symptoms of cluster headaches?

Cluster headaches are headaches that come in groups (clusters) lasting weeks or
months, separated by pain-free periods of months or years.

 During the period in which the cluster headaches occur, pain typically
occurs once or twice daily, but some patients may experience pain more
than twice daily.
 Each episode of pain lasts from 30 to 90 minutes.
 Attacks tend to occur at about the same time every day and often awaken
the patient at night from a sound sleep.
 The pain typically is excruciating and located around or behind one eye.
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 Some patients describe the pain as feeling like a hot poker in the eye. The
affected eye may become red, inflamed, and watery.
 The nose on the affected side may become congested and runny.

Unlike patients with migraine headaches, patients with cluster headaches tend to
be restless. They often pace the floor, bang their heads against a wall, and can be
driven to desperate measures. Cluster headaches are much more common in
men than women.
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Circle of Willis: 2 Vertebral Arteries join and form basilar artery, continues to
the posterior cerebral arteries, continues to ICA (internal carotid artery) that
bifurcates to middle cerebral and anterior cerebral. Posterior cerebral
communicates with the ICA via the posterior communicating. The left ICA
communicates with the right ICA with the anterior communicating
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Stroke is defined as an acute neurological deficit lasting more than 24

hours and caused by cerebrovascular aetiology. It is subdivided into
ischaemic stroke (caused by vascular occlusion or stenosis) and
haemorrhagic stroke (caused by vascular rupture, resulting in intra-
parenchymal and/or subarachnoid haemorrhage). Ischaemic stroke
accounts for about 85% of cases and haemorrhagic stroke about 15%. [1]
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Stroke is the third leading cause of death in most resource-rich countries and a
major cause of disability. A transient ischaemic attack (TIA), colloquially termed
a 'mini stroke', is a brief episode of neurological dysfunction caused by focal
brain or retinal ischaemia, with clinical symptoms typically lasting <1 hour and
without evidence of acute infarction
 Cerebral ischaemia should be suspected when a patient presents with
typical symptoms of rapidly resolving unilateral weakness or numbness,
but also with less classic symptoms such as unilateral vision loss,
transient aphasia, or vertigo.
 In a patient who presents with ongoing neurological deficit, aggressive
treatment for stroke should not be delayed in the hope that the symptoms
will spontaneously resolve.
 Treatment focuses on work-up of underlying aetiology and secondary
prevention with anticoagulants in cases of embolic aetiology, or
antiplatelet therapy for non-embolic events. Modifiable risk factors such
as carotid stenosis, hypertension, hare lipped, and unhealthy lifestyle are
other targets of therapy.
 Transient ischaemia attacks (TIAs) have considerable risk of early
recurrent cerebral ischaemic events. Evaluation and initiation of
secondary prevention should occur rapidly.
 In addition to a complete neurological examination and evaluation for
diseases that mimic TIA, diagnostic imaging such as MRI with diffusion-
weighted images is helpful to detect evidence of cerebral ischaemia.

ABCD2 algorithm(1) predicts a patient's very early risk of stroke following a TIA.

The score is calculated according to 5 important clinical features:

Symbol Clinical feature Criterion Point

A Age >= 60 1
B Blood pressure >= 140/90 mmHg 1
C Clinical features of the TIA unilateral weakness 2
speech disturbance without weakness 1
D1 Duration of symptoms >= 60 min 2
10-59 min 1
<10 min 0
D2 Diabetes diagnosed with diabetes? 1

The corresponding 2 day risks for a subsequent stroke are:

ABCD2 score Risk of stoke at 2 days

0-3 1%
4-5 4%
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6-7 8%

Ischaemic Stroke

Regardless of the specific aetiology, ischaemic stroke occurs when blood supply
in a cerebral vascular territory is critically reduced due to occlusion or critical
stenosis of a cerebral artery. A minority of ischaemic strokes are caused by
cerebral sinus or cortical vein thrombosis. Risk factors strongly associated with
ischaemic stroke are smoking, [3] diabetes, [4] atrial fibrillation, [5] comorbid
cardiac conditions, [6] carotid artery stenosis, [7] [8] [9] and sickle cell disease.
[10]

Haemorrhagic stroke

Intra-cerebral haemorrhage is caused by vascular rupture with bleeding into the

brain parenchyma. Three-quarters of haemorrhagic strokes are intra-cerebral
haemorrhage, with the rest being subarachnoid haemorrhage. Strong risk factors
are anticoagulation, [11] [12] sympathomimetic drug abuse, [13] and vascular
malformations. [14]

Intracerebral haemorrhage is caused by vascular rupture with bleeding into the

brain parenchyma. The expanding haematoma may shear additional
neighbouring arteries, resulting in further bleeding and haematoma expansion.
[7] Eventually haematoma growth is halted by a combination of haemostasis and
increased pressure. Significant haematoma growth (30% to 40% increase) over
several hours following presentation is common in those who present within 3
to 4 hours of the onset of symptoms. [8] The period of bleeding may be extended
even longer in anticoagulated patients. Arresting haematoma growth is therefore
a key objective for medical or surgical therapies. As a consequence of
haematoma growth, the haemorrhage may rupture into the subarachnoid space
or the intraventricular space. Mortality is increased when intraventricular
haemorrhage is present, in part due to the associated increased risk of
communicating or non-communicating hydrocephalus. [9] Mortality from
intracerebral haemorrhage is high and may result from direct destruction of
critical brain areas, compression of critical brain areas by adjacent haematoma,
or cerebral circulatory arrest caused by globally increased intracranial pressure.

Transient ischaemic attack

The population-wide prevalence of transient ischaemic attack (TIA)

symptoms in adults is approximately 2.3%. [15] Strong risk factors for TIA
are atrial fibrillation, [16] [17] valvular disease, [17] carotid stenosis, [18]
congestive heart failure, [17] hypertension, [16] [17] diabetes mellitus,
[19] [20] cigarette smoking, [16] [21] and alcohol abuse. [22]
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The severity of clinical neurological impairment after arterial occlusion depends

on the complex interplay between the degree of obstruction, area and function of
tissue supplied by the vessel, the length of time thrombus obstructs the vessel,
and the ability of collateral circulation to provide supplemental perfusion to the
area at risk.
Under normal circumstances, cerebral blood flow (CBF) is tightly autoregulated
to maintain a blood flow of >50 mL/100 g/minute across a wide range of
cerebral perfusion pressures by alteration in cerebrovascular resistance. [16] If
the CBF falls to between 20 and 50 mL/100 g/minute, the brain can compensate
by increasing oxygen extraction, but below this threshold, neuronal quiescence
occurs with neurological deficits. Below 15 mL/100 g/minute of CBF, neuronal
death occurs. Thus, if there is complete loss of cerebral blood flow, then neuronal
death will occur rapidly. With partial blood flow, neuronal function is impaired,
but cell death will be delayed by minutes to hours. Restoration of flow,
presumably via autolysis of the occluding thrombus, can arrest the progression
to infarction.
Early in the process of ischaemic neuronal injury, cytotoxic oedema causes influx
of water to the intracellular space, which is observable as hyperintensity on MRI
diffusion images. [2] Experimental data from animal models suggests that middle
cerebral artery occlusion lasting 15 minutes or less creates little evidence of
injury, whereas by 2 hours the downstream infarct is essentially complete. [17]
As predicted by this model, in humans, the likelihood of spontaneous recovery
from a neurological deficit falls as the symptom duration lengthens. If symptoms
are present at 3 hours, the likelihood of being completely asymptomatic at 24
hours is only 2%. [3] This is part of the rationale for not withholding
thrombolysis for acute neurological symptoms in the hopes of spontaneous
resolution.

Cerebral aneurysm

An acquired focal abnormal dilation of the wall of an artery in the brain. Autopsy
studies indicate that cerebral aneurysms are fairly common in adults, with a
prevalence ranging between 1% and 5%. [23] Strong risk factors include
smoking, alcohol consumption, family history of subarachnoid haemorrhage,
previous subarachnoid haemorrhage, and heritable connective tissue disease
(specifically in patients with autosomal dominant polycystic kidney disease,
Ehlers-Danlos syndrome type IV, neurofibromatosis type 1, and Marfan's
syndrome). [24] [25]

Pathophysiology
Blood vessels are composed of three layers: tunica intima, tunica media
(muscularis), and tunica externa (adventitia). The intima and media are
separated by the lamina elastica interna, and the media and adventitia are
separated by the membrana elastica externa. In cerebral vessels the media is
thinner and the membrana elastica externa is negligible.
Although the pathophysiology of traumatic and infectious cerebral aneurysms is
obvious, that of spontaneous saccular aneurysms is less clear. Hypertension and
smoking are thought to contribute significantly to the vascular changes
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associated with saccular cerebral aneurysms. [6] One hypothesis relates to the
effect cigarette smoking has on inhibitors of proteases, which results in
degradation of various connective tissues, including arterial walls. [11] In
pathology specimens, the tunica media is decreased and the aneurysm sac is
therefore reduced to a single layer of endothelial cells and a thin fibrous layer.
The lamina elastica interna ends at the entrance to the aneurysm sac. [12]
Continuous arterial pressure directed on this abnormal section of the artery
leads to aneurysmal out-pouching, particularly at arterial branch points, where
the pressure is higher. [6]
With increased availability and improved sensitivity of non-invasive cerebral
imaging techniques, more unruptured cerebral aneurysms are being detected.
Although they are often discovered incidentally, unruptured aneurysms can
cause symptoms through the mass effect on neighbouring cranial nerves or brain
parenchyma.

Subarachnoid haemorrhage

A medical emergency where there is bleeding into the subarachnoid space. The
most common cause of non-traumatic subarachnoid haemorrhage is intra-
cranial aneurysm. Strong risk factors include hypertension, smoking, family
history, and autosomal polycystic kidney disease. [26]

Pathophysiology

Cerebral aneurysms arise at the bifurcation of major arteries that form the circle
of Willis. The majority are located at the anterior communicating/anterior
cerebral artery junction (Acom/ACA), distal internal carotid
artery/posterior communicating artery junction (ICA/Pcom), and middle
cerebral artery bifurcation (MCA). Less than 10% arise from the vertebral or
basilar arteries. Up to 19% of patients are found to have multiple aneurysms. [9]
[10] Greater pressures at the apexes of arterial bifurcation, pulsatile flow
patterns, and turbulence have been suggested as explanations for the
predilection of aneurysm growth at these sites. [15]

The risk of aneurysm rupture depends on its size, location, the presence of
symptoms, the presence of multiple aneurysms, and whether previous
aneurysms have ruptured. [15] [18] [19] [20] [21] [22] [23] [24] Patient-related
predictors of rupture are age and smoking. Small, asymptomatic aneurysms (less
than 7 mm) are less prone to rupture than bigger ones that exert mass effect on
surrounding structures. Aneurysms located at the basilar tip, in the
vertebrobasilar, posterior cerebral distribution, or posterior part of the circle of
Willis are more likely to rupture compared with aneurysms in other locations.
[19] [20] [25] The 5-year cumulative rupture rate of an aneurysm less than 7
mm in diameter is 0% when located on ICA, Acom, or MCA and 2.5% when
located on Pcom or posterior cerebral, vertebral, or basilar arteries. [25] An
unruptured aneurysm discovered during work-up for SAH (caused by a different
aneurysm) has a higher annual incidence of rupture than a single unruptured
aneurysm. [15] [21] [22] In this case, the 5-year cumulative rupture rate ranges
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between 1.5% and 3.4% for aneurysms less than 7 mm and between 2.6% and
18.4% for aneurysms between 7 mm and 24 mm.

Treatment approach
SAH requires emergency treatment and early referral to the intensive care unit
(ICU). [55] [56] When patients are evaluated in rural or community settings,
strong consideration should be made for expedited referral to a tertiary care
centre.
Stabilisation
Stabilisation of patients simultaneously with work-up is vital to prevent
unwanted early complications. It is essential to establish the need for
endotracheal intubation and mechanical ventilation as the first priority. [33]
Consciousness level should be assessed using the Glasgow Coma Scale (GCS), in
addition to airway adequacy and cardiovascular function. A poor level of
awareness and seizures on presentation are risk factors for aspiration. A full
neurological examination should be performed with special attention to
pupillary reaction. Isolated dilation of one pupil and loss of the pupillary light
reflex may indicate brain herniation as a result of rising intracranial pressure. A
poor neurological status on admission seems to predict cardiac abnormalities
thought to be secondary to overwhelming sympathetic activation. [34] [35] [36]
[37] Close monitoring of vital signs should be instituted (e.g., BP, heart rate and
rhythm, and respiratory rate). [38] Blood pressure should be monitored and
controlled to balance the risk of stroke, hypertension-related rebleeding, and
maintenance of cerebral perfusion pressure. [55]

Electrolytes and coagulation

Electrolyte imbalances (e.g., hyponatraemia) are common and should be
corrected. If present, coagulopathy should be treated aggressively using fresh
frozen plasma and vitamin K.

Analgesia
Headache should be treated with opioid analgesics; however, mental status also
needs be closely followed, especially in patients monitored for acute
hydrocephalus or vasospasm. Judicious use of analgesia is therefore
recommended.

Anticonvulsants
The effect of convulsions on patients with SAH is unknown. Despite widespread
use in the US, the practice of prophylactic anticonvulsants is unsettled. A
retrospective study suggested that a short course of perioperative phenytoin is
associated with fewer side effects without increasing the risk of seizures. [57]

Calcium-channel blockers
Calcium-channel blockers should be started on admission for vasospasm
prophylaxis. They reduce risk of poor outcome and secondary ischaemia after
aneurysmal SAH. [B Evidence]

Post stabilisation
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The patient should be admitted to an ICU, ideally a neurological and

neurosurgical ICU, once stabilised. These units significantly reduce in-hospital
mortality and length of stay. [58] On admission to ICU, neurological status should
be graded using scales such as the Hunt and Hess Scale or the World Federation
of Neurological Surgeons Scale. The higher the grade, the poorer the outcome.
[59] The Fisher Scale can be used to document and grade the quantity and
distribution of subarachnoid blood on admission CT. [54] Although not
definitive, it helps to predict the potential risk of vasospasm, which is a serious
complication.

Antitussives and stool softeners

Cough should be suppressed with antitussives to prevent potential rebleeding.
Stool softeners are used routinely, as straining to defecate can potentially cause
rebleeding.

Surgery and coil embolisation

A neurosurgeon and interventional neuroradiologist should be involved in the
decision about how to treat an aneurysm. Most surgeons operate on patients
with good neurological status during the first 72 hours to prevent rebleeding.[C
Evidence] Young age and normal preoperative level of consciousness are
associated with favourable operative results and better recovery. [9] [10]
Controversy exists over the choice between surgical clipping and endovascular
coil embolisation. [C Evidence] The results of a major international prospective
and randomised trial have sparked major controversies. [60] [61] [62] The
International Subarachnoid Aneurysm Trial (ISAT) included over 1000 patients
in each treatment group. At 1 year, 23.7% of patients were dead or dependent
following coiling compared with 30.6% in the clipping group. [61] Criticisms of
the study included uneven distribution of enrolled patients (almost all came
from Europe), differing levels of expertise among the interventionists and
surgeons, and enrolment criteria that aneurysms be considered suitable for
either surgical or endovascular repair. [60] Long-term follow-up of patients
enrolled in ISAT has revealed that despite an increased risk of recurrent bleeding
in the coiling group, the 5-year death risk remained significant compared with
the clipping group. [63]
Surgical clipping or endovascular coil embolisation are needed to secure the
aneurysm. In surgical clipping, a craniotomy is performed to expose the
aneurysm, and a clip is placed on its neck to exclude it from the circulation. A
craniotomy is not needed for endovascular coil embolisation. An arterial catheter
is advanced to the aneurysm lumen where titanium coils are deposited. A
thrombus forms in the lumen, excluding the aneurysm from the circulation.
Major drawbacks to this procedure are incomplete embolisation and recurrences
requiring reintervention. [64] [65] [66] [67] Potential adverse events of the
procedure itself are stroke, vessel rupture, and dissection.
Coiling may be a better option in elderly patients with comorbid diseases and
high surgical risks, basilar tip aneurysms, and small aneurysms with small necks
located in the anterior communicating artery. Middle cerebral artery and
posterior communicating artery aneurysms, as well as wide-neck aneurysms, are
better suited for surgical clipping. There are no guidelines or official
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recommendations, but these characteristics are widely accepted in the

neurosurgical and endovascular community in the US.

Ischaemic stroke

Pathophysiologically, ischaemic stroke can be broadly classified as:

 Primary vascular pathologies (e.g., atherosclerosis, arterial dissection,
migraine, or vasculitis) that directly reduce cerebral perfusion and/or
result in artery-to-artery embolism (i.e., stenosis or occlusion of a distal
artery by an embolus originating in a proximal artery)
 Cardio-aortic pathologies (e.g., atrial fibrillation, myocardial
ischaemia/infarction, patent foramen ovale, aortic arch atherosclerosis)
that lead to cerebral arterial occlusion due to embolism
 Haematological pathologies (e.g., prothrombotic hypercoagulable or
hyperaggregable states) that directly precipitate cerebrovascular
thrombosis (particularly venous), or facilitate systemic venous or
intracardiac thrombus formation and cardioembolism.

History & exam

Key factors

 vision loss or visual field deficit

 weakness
 aphasia
 impaired co-ordination (ataxia)

Other diagnostic factors

 hx TIA
 sudden onset of symptoms
 negative symptoms (i.e., loss of function)
 altered sensation
 vertigo/dizziness
 nausea and/or vomiting
 headache
 neck or facial pain
 diplopia
 sensory loss
 dysarthria
 gaze paresis
 meiosis, ptosis, and facial anhidrosis (hemilateral)
 altered level of consciousness/coma
 confusion
 arrhythmias, murmurs, or pulmonary oedema
 24

History & exam details

Diagnostic tests

1st tests to order

 CT head
 MRI brain
 serum glucose
 serum electrolytes
 serum urea and creatinine
 cardiac enzymes
 ECG
 FBC
 prothrombin time (PT) and PTT (with international normalised ratio)

Tests to consider

 serum toxicology screen

 stool guaiac test
 CXR
 CT angiography
 MR angiography
 CT or MR venography
 carotid ultrasound
 transcranial Doppler ultrasound
 conventional (invasive) angiography

Emerging tests

 CT perfusion or MRI perfusion-weighted imaging

Diagnostic tests details

Treatment details

Acute

without cerebral venous sinus thrombosis

 presentation within 4.5 hours and no contraindication to

thrombolysis
o alteplase (tissue plasminogen activator or tPA)
o aspirin 24 hours after tPA
o supportive care
o swallowing assessment
o DVT prophylaxis + early mobilisation
 presentation after 4.5 hours or contraindication to thrombolysis
o aspirin
o supportive care
o swallowing assessment
 25

o DVT prophylaxis + early mobilisation

with cerebral venous sinus thrombosis

 anticoagulation
 supportive care
 swallowing assessment

Treatment approach

The goals of treatment of acute ischaemic stroke are to restore blood flow,
support energy metabolism in ischaemic tissue, treat complications of stroke-
related oedema, and prevent common acute medical complications. Rapid
evaluation and diagnosis is the cornerstone of successful ischaemic stroke
therapy. CT or MRI scan is mandatory to exclude intracerebral haemorrhage and
stroke mimics. The absence of signs on CT does not exclude acute ischaemic
stroke. Following assessment of airway, breathing, and circulation, the next step
is to consider whether reperfusion can be achieved.

Intravenous thrombolysis

Alteplase (tissue plasminogen activator or tPA) promotes thrombolysis and

thereby re-canalisation and re-perfusion.[C Evidence] Based on new clinical
trials utilising alteplase for thrombolysis in patients with acute ischaemic stroke
and no contraindications, the window of opportunity for treatment of these
patients is 4.5 hours after the onset of neurological symptoms. [53] [A Evidence]
Goal time between emergency department arrival and start of CT scan is 25
minutes, and from emergency department arrival to initiation of intravenous tPA
(if indicated) is 60 minutes. [42]

Information regarding the benefits and risks of tPA treatment should be given to
the patient, if competent, or to a surrogate decision-maker, if present. Verbal or
written consent should be obtained if feasible. In the frequent situation where
the patient is not competent to make medical decisions, and family or a
surrogate decision-maker cannot be identified or approached in a timely
manner, the physician should substitute his or her judgment. Decision-makers
should be informed of the overall 6% risk of brain haemorrhage, of which
approximately half are fatal. They should also be informed that despite this risk
people treated with tPA are more likely to do better. Overall 1 in 8 people treated
with tPA have a complete or near-complete recovery who otherwise would have
been disabled; this statistic is the number needed to treat. [54]

Candidates for intravenous thrombolysis with tPA

American Heart Association guidelines state that patients could be treated with
tPA when: [45]
 26

 There is measurable neurological deficit, which does not resolve

spontaneously
 The symptoms of stroke are not suggestive of subarachnoid haemorrhage
 There is no evidence of cerebral venous sinus thrombosis
 Onset of symptoms ≤4.5 hours
 There is no hx head trauma or prior stroke in the previous 3 months
 There is no hx MI in the previous 3 months
 There is no hx GI or urinary tract haemorrhage in the previous 21 days
 There is no hx major surgery in the previous 14 days
 There is no hx arterial puncture at a non-compressible site in the
previous 7 days
 There is no hx previous intracranial haemorrhage
 BP is not elevated at time of infusion (systolic ≤185 mmHg and diastolic
≤110 mmHg); however, if BP can be pharmacologically lowered and
remains stable, then tPA can still be considered if still within the 4.5-hour
time window
 There is no evidence of active bleeding or acute trauma (fracture) on
examination
 Not taking an oral anticoagulant or, if anticoagulant being taken, INR ≤1.7
 If receiving heparin in previous 48 hours, activated PTT must be in
normal range
 Platelet count ≥100,000 mm^3
 Blood glucose concentration >2.8 mmol/L (>50 mg/dL)
 There is no hx seizure with postictal residual neurological impairments
 CT does not show a multi-lobar infarction (hypodensity >1/3 volume of
cerebral hemisphere)
 The patient or family members understand the potential risks and
benefits of treatment.

Caution should be exercised in treating a patient with major deficits, as the

likelihood of favourable outcome is reduced with major neurological deficits, and
there is increased risk of haemorrhage following thrombolysis in these patients.
[45] [55]

Aspirin

Ischaemic stroke patients should receive aspirin.[B Evidence] However, if tPA is

given, aspirin should not be started for 24 hours, and only then after a head CT
shows the absence of intracranial haemorrhage. Two randomised trials of
aspirin for acute ischaemic stroke have shown a trend towards better outcomes
in the aspirin arm. [56] [57] Non-aspirin antiplatelet drugs, including
dipyridamole, clopidogrel, and platelet glycoprotein IIb/IIIa inhibitors, have not
been studied in acute stroke and therefore in general are not indicated. However,
these medicines may be useful in the secondary prevention of stroke. [58]

Anticoagulation

Urgent anticoagulation in unselected ischaemic stroke patients, with the goal of

improving acute stroke outcomes, is generally not recommended.[B Evidence]
 27

Meta-analyses fail to show reduction in stroke disability in acute ischaemic

stroke patients treated with anticoagulants but do show an increase in the risk of
haemorrhagic transformation of stroke, particularly in patients with larger
stroke volumes. [59]

Anticoagulation is, however, first-line therapy for cerebral venous sinus

thrombosis (as identified on imaging), even in the presence of haemorrhagic
transformation of the infarction. [55] Anticoagulation should be continued for
3 to 6 months. In the absence of progressive symptoms, patients may be
transitioned to warfarin in the acute period, with target INR 2.0 to 3.0.
Aspirin and tPA are not indicated in these patients.

Supportive care

At the same time as the acute evaluation for reperfusion therapies, steps should
be taken to support blood oxygenation, [45] [60] and systemic BP, [61] [B
Evidence] and to avoid hypo/hyperglycaemia, [62] [63] [64] and fever. [45] [65]
[66] These steps, while not shown to be effective by clinical trials, may retard
stroke evolution or prevent stroke extension by optimising energy substrate
delivery and tissue energy metabolism.

Following emergency department evaluation and treatment, patients with

ischaemic stroke should be transferred to a dedicated stroke unit. These units
have been shown in controlled and non-controlled trials to improve stroke
functional outcome and survival. [67] [B Evidence]

Nutritional support, rehabilitation therapy (physical, occupational and/or

speech therapy as indicated), prevention of aspiration (swallowing assessment),
and prevention of deep venous thromboembolism (usually with heparin) are all
required in the sub-acute phase of hospital care.

Treatment details

Therapeutic hypothermia is defined as an intentionally induced, controlled

reduction of a patient’s core temperature below 36°C. Further classification
delineates mild (34°C–35.9°C), moderate (32°C–33.9°C), moderate/ deep (30°C–
31.9°C), or deep (< 30°C) hypothermia.32 Ischemia produces variable degrees of
tissue damage, with apoptosis and cellular death as the final common pathways
of a multifactorial process. Brain tissue ischemia leads to ATP depletion within a
very short period of time. The exhaustion of ATP triggers membrane
depolarization from an uncontrolled influx of ions in the setting of
nonoperational Na+-K+ ATPase pumps. Changes in membrane potentials release
EAAs and promote Ca influx. Excess intracellular Ca initiates mitochondrial
injury. Affected mitochondria produce oxygen free radicals, and release
cytochrome C, causing activation of caspase mediated DNA fragmentation and
cellular apoptosis. If reperfusion occurs, the injured mitochondria may further
contribute to neuronal damage. Likewise, an influx of in tissue necrosis on
 28

restoration of blood flow.5,20,23,28,31,48 Experimental animal studies have

demonstrated that hypothermia effectively targets a multitude of ischemia
induced pathways. These processes, which are invariably detrimental to
sustained cellular activity, include energy depletion, ion shifts, free radical
formation, EAA release, and inflammation.3,44,47 Hypothermia reduces cerebral
oxygen consumption by a rate of approximately 6% per 1°C change in
temperature, allowing preservation of potentially viable brain tissue for longer
periods of time.9,47 Lowering brain temperature expedites restoration of ionic
homeostasis and impedes ischemia-induced EAA release.30,35,41,42
Furthermore, free radical formation and inflammatory responses are inhibited
during hypothermia. Thus, hypothermia counteracts multiple steps of cellular
injury to reduce the recruitment of penumbral tissue into the ischemic core
following acute stroke.
29
 30

Cerebellum
1) archicerebellum=flocculus and nodule = fastigial. Archicerebellum has
extensive comms with vestibular nuclei function is balance
2) paleocerebellum=vermisglobose and emboliform. Paleocerebellum
has extensive communication with the spinal cordfunction is muscle
tone and posture
3) neocerebellum=cerebral hemispheres associated nucleus=dendate
nucleus. Neocerebellum has extensive comms with the cortex and basal
ganglia function is coordination of movement.
31
 32

Autoregulation of cerebral blood flow

Cerebral perfusion pressure, or CPP, is the net pressure gradient causing
blood flow to the brain (brain perfusion). It must be maintained within narrow
limits because too little pressure could cause brain tissue to become ischemic
(having inadequate blood flow), and too much could raise intracranial pressure
(ICP).

From resistance

CPP can be defined as the pressure gradient causing cerebral blood flow (CBF)
such that

where:

CVR is cerebrovascular resistance

By intracranial pressure

An alternative definition of CPP is:[1]

where:
 33

MAP is mean arterial pressure

ICP is intracranial pressure

Issue 8 (1998) Article 4: Page 3 of 4 Go to page: 1 2 3 4

Intracranial Pressure and Cerebral Blood Flow (Continued)

Cerebral Blood Flow

The normal cerebral blood flow is 45-50ml 100g-1 min-1, ranging from
20ml 100g-1 min-1 in white matter to 70ml 100g-1 min-1 in grey matter. There are
two essential facts to understand about cerebral blood flow. Firstly, in normal
circumstances when the flow falls to less than 18-20ml 100g-1 min-1,
physiological electrical function of the cell begins to fail. Secondly, an increase or
decrease in CBF will cause an increase or decrease in cerebral arterial blood
volume because of arterial dilatation or constriction. Thus in a brain which is
decompensated as a result of major intracranial pathology, increases or
decreases in CBF will in turn lead to a significant rise or fall in ICP. The
physiological factors which can alter CBF and hence ICP are listed in Table
2. There are also a number of drugs which can induce arterial dilatation, the
most well known being high concentrations of volatile agents. These will be
discussed in detail in a subsequent article.

Teaching Point. There are a number of physiological factors which affect or

change cerebral blood flow (CBF). Rises in CBF due to hypoxia, hypercapnia
(raised blood CO2) and high concentrations of volatile agents will cause a rise in
ICP once the normal compensating mechanisms have been exhausted. Poor
anaesthetic technique during which hypoxia, hypercapnia and hypotension occur
will seriously damage the critically ill brain further.

Autoregulation. CBF is maintained at a constant level in normal brain in the face

of the usual fluctuations in blood pressure by the process of autoregulation. It is
a poorly understood local vascular mechanism. Normally autoregulation
maintains a constant blood flow between MAP 50 mmHg and 150 mmHg.
However in traumatised or ischaemic brain, or following vasodilator agents
(volatile agents and sodium nitroprusside) CBF may become blood pressure
dependent. Thus as arterial pressure rises so CBF will rise causing an increase in
cerebral volume. Similarly as pressure falls so CBF will also fall, reducing ICP, but
also inducing an uncontrolled reduction in CBF.

More recent work has shown that following trauma autoregulation may still be
functioning. Bouma reported that it was present in up to 69% patients with head
injuries [5].

Brain Stem Death

 34

Diagnosis

In the UK, the formal rules for the diagnosis of brain stem death have undergone
only minor modifications since they were first published [6] in 1976. The most
recent revision of the UK's Department of Health Code of Practice governing use
of that procedure for the diagnosis of death [1] reaffirms the preconditions for its
consideration. These are:

1. There should be no doubt that the patient’s condition - deeply comatose,

unresponsive and requiring artificial ventilation - is due to irreversible
brain damage of known aetiology.
2. There should be no evidence that this state is due to depressant drugs.
3. Primary hypothermia as the cause of unconsciousness must have been
excluded, and
4. Potentially reversible circulatory, metabolic and endocrine disturbances
likewise.
5. Potentially reversible causes of apnoea (dependence on the ventilator),
such as muscle relaxants and cervical cord injury, must be excluded.

With these pre-conditions satisfied, the definitive criteria are:

1. Fixed pupils which do not respond to sharp changes in the intensity of

incident light.
2. No corneal reflex.
3. Absent oculovestibular reflexes – no eye movements following the slow
injection of at least 50ml of ice-cold water into each ear in turn (the
caloric reflex test).
4. No response to supraorbital pressure.
5. No cough reflex to bronchial stimulation or gagging response to
pharyngeal stimulation.
6. No observed respiratory effort in response to disconnection of the
ventilator for long enough (typically 5 minutes) to ensure elevation of the
arterial partial pressure of carbon dioxide to at least 6.0 kPa (6.5 kPa in
patients with chronic carbon dioxide retention). Adequate oxygenation is
ensured by pre-oxygenation and diffusion oxygenation during the
disconnection (so the brain stem respiratory centre is not challenged by
the ultimate, anoxic, drive stimulus). It should be noted this is a
dangerous - potentially lethal – test.[9][10]

Two doctors, of specified status and experience, are required to act together to
diagnose death on these criteria and the tests must be repeated after “a short
period of time … to allow return of the patient’s arterial blood gases and baseline
parameters to the pre-test state”. These criteria for the diagnosis of death are not
applicable to infants below the age of two months

Doll’s eyes
 35

The vestibulo-ocular reflex (VOR) is a reflex eye movement that stabilizes

images on the retina during head movement by producing an eye movement in
the direction opposite to head movement, thus preserving the image on the
center of the visual field. For example, when the head moves to the right, the
eyes move to the left, and vice versa. Since slight head movement is present all
the time, the VOR is very important for stabilizing vision: patients whose VOR is
impaired find it difficult to read using print, because they cannot stabilize the
eyes during small head tremors. The VOR does not depend on visual input and
works even in total darkness or when the eyes are closed. However, in the
presence of light, the fixation reflex is also added to the movement

Testing

This reflex can be tested by the Rapid head impulse test or Halmagyi-Curthoys-
test, in which the head is rapidly moved to the side with force, and is controlled if
the eyes succeed to remain looking in the same direction. When the function of
the right balance system is reduced, by a disease or by an accident, quick head
movement to the right cannot be sensed properly anymore. As a consequence, no
compensatory eye movement is generated, and the patient cannot fixate a point
in space during this rapid head movement.

Another way of testing the VOR response is a caloric reflex test, which is an
attempt to induce nystagmus (compensatory eye movement in the absence of
head motion) by pouring cold or warm water into the ear. Also available is bi-
thermal air caloric irrigations, in which warm and cool air is administered into
the ear.

Comatose patients

In comatose patients, once it has been determined that the cervical spine is
intact, a test of the vestibulo-ocular reflex can be performed by turning the head
to one side. If the brainstem is intact, the eyes will move conjugately away from
the direction of turning (as if still looking at the examiner rather than fixed
straight ahead). This is how a doll's eyes would move. So having "doll's eyes" is a
sign that a comatose patient's brainstem is still intact.

Typically the doll's eyes reflex is elicited by turning the head of the unconscious patient while obser
eyes will normally move as if the patient is fixating on a stationary object. If there is a negative doll
the eyes remain stationary with respect to the head.

The doll's eyes reflex may be tested in the conscious subject when determining the aetiology of a ga
the lesion is "nuclear" or "supranuclear". If there is damage to brainstem gaze centres then volunt
movements are reduced. If there is damage to the cortical gaze centre then voluntary movement is
eyes reflex is retained.

The reflex may be suppressed in the normal conscious subject.

 36

If the doll's eye reflex is absent then there is a lesion in the following pathway:

 the labyrinth and vestibular nerve

 the neck proprioceptors
 cranial nerves 3 and 6
 the external ocular muscles

The normal doll's eyes reflex is NOT dependent on visual fixation of a stationary object, indee
comatose patients who are blind or in the dark.

Glasgow Coma Scale

The Glasgow Coma Scale provides a score in the range 3-15; patients with scores
of 3-8 are usually said to be in a coma. The total score is the sum of the scores in
three categories. For adults the scores are as follows:

Spontaneous--open with blinking at

4 points
baseline
Eye Opening Response Opens to verbal command, speech, or shout 3 points
Opens to pain, not applied to face 2 points
None 1 point
Oriented 5 points
Confused conversation, but able to answer
4 points
questions
Verbal Response
Inappropriate responses, words discernible 3 points
Incomprehensible speech 2 points
None 1 point
Obeys commands for movement 6 points
Purposeful movement to painful stimulus 5 points
Withdraws from pain 4 points
Motor Response Abnormal (spastic) flexion, decorticate
3 points
posture
Extensor (rigid) response, decerebrate
2 points
posture
None 1 point

For children under 5, the verbal response criteria are adjusted as follow

SCORE 2 to 5 YRS 0 TO 23 Mos.

Appropriate words or
5 Smiles or coos appropriately
phrases
4 Inappropriate words Cries and consolable
 37

Persistent cries and/or Persistent inappropriate crying &/or

3
screams screaming
2 Grunts Grunts or is agitated or restless
1 No response No response

Intracranial pressure (ICP) is the pressure inside the skull and thus in the
brain tissue and cerebrospinal fluid (CSF). The body has various mechanisms by
which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in
normal adults through shifts in production and absorption of CSF. CSF pressure
has been shown to be influenced by abrupt changes in intrathoracic pressure
during coughing (intraabdominal pressure), valsalva (Queckenstedt's
maneuver), and communication with the vasculature (venous and arterial
systems). ICP is measured in millimeters of mercury (mmHg) and, at rest, is
normally 7–15 mmHg for a supine adult, and becomes negative (averaging
−10 mmHg) in the vertical position.[1] Changes in ICP are attributed to volume
changes in one or more of the constituents contained in the cranium.

Intracranial hypertension, commonly abbreviated IH, IICP or raised ICP, is

elevation of the pressure in the cranium. ICP is normally 7–15 mm Hg; at 20–
25 mm Hg, the upper limit of normal, treatment to reduce ICP may be needed.

The Monro-Kellie hypothesis

The pressure-volume relationship between ICP, volume of CSF, blood, and brain
tissue, and cerebral perfusion pressure (CPP) is known as the Monro-Kellie
doctrine or the Monro-Kellie hypothesis.[3][4][5]

The Monro-Kellie hypothesis states that the cranial compartment is

incompressible, and the volume inside the cranium is a fixed volume. The
cranium and its constituents (blood, CSF, and brain tissue) create a state of
volume equilibrium, such that any increase in volume of one of the cranial
constituents must be compensated by a decrease in volume of another.[5]

The principal buffers for increased volumes include both CSF and, to a lesser
extent, blood volume. These buffers respond to increases in volume of the
remaining intracranial constituents. For example, an increase in lesion volume
(e.g. epidural hematoma) will be compensated by the downward displacement of
CSF and venous blood.[5] These compensatory mechanisms are able to maintain a
normal ICP for any change in volume less than approximately 100–120 mL.[citation
needed]

Increased ICP

Severely high ICP can cause the brain to herniate.

 38

One of the most damaging aspects of brain trauma and other conditions, directly
correlated with poor outcome, is an elevated intracranial pressure. [6] ICP is very
likely to cause severe harm if it rises too high.[7] Very high intracranial pressures
are usually fatal if prolonged, but children can tolerate higher pressures for
longer periods.[8] An increase in pressure, most commonly due to head injury
leading to intracranial hematoma or cerebral edema can crush brain tissue, shift
brain structures, contribute to hydrocephalus, cause the brain to herniate, and
restrict blood supply to the brain.[9] It is a cause of reflex bradycardia.[10]

Pathophysiology

The cranium and the vertebral canal, along with the relatively inelastic dura,
form a rigid container, such that the increase in any of its contents; brain, blood,
or CSF, will tend to increase the ICP. In addition, any increase in one of the
components must be at the expense of the other two; this relationship is known
as the Monro-Kellie doctrine. Small increases in brain volume do not lead to
immediate increase in ICP because of the ability of the CSF to be displaced into
the spinal canal, as well as the slight ability to stretch the falx cerebri between
the hemispheres and the tentorium between the hemispheres and the
cerebellum. However, once the ICP has reached around 25 mmHg, small
increases in brain volume can lead to marked elevations in ICP; this is due to
failure of intracranial compliance.

Traumatic brain injury is a devastating problem with both high subsequent

morbidity and high mortality. Injury to the brain occurs both at the time of the
initial trauma (the primary injury) and subsequently due to ongoing cerebral
ischemia (secondary injury). Cerebral edema, CSF hypertension, circulatory
hypotension, and hypoxic conditions are well recognized causes of this
secondary injury. In the intensive care unit, raised intracranial pressure
(intracranial hypertension) is seen frequently after a severe diffuse brain injury
(one that occurs over a widespread area) and leads to cerebral ischemia by
compromising cerebral perfusion.

Cerebral perfusion pressure (CPP), the pressure of blood flowing to the brain, is
normally fairly constant due to autoregulation, but for abnormal mean arterial
pressure (MAP) or abnormal ICP the cerebral perfusion pressure is calculated by
subtracting the intracranial pressure from the mean arterial
pressure: CPP = MAP − ICP .[1][11] One of the main dangers of increased ICP is that
it can cause ischemia by decreasing CPP. Once the ICP approaches the level of the
mean systemic pressure, cerebral perfusion falls. The body’s response to a fall in
CPP is to raise systemic blood pressure and dilate cerebral blood vessels. This
results in increased cerebral blood volume, which increases ICP, lowering CPP
further and causing a vicious cycle. This results in widespread reduction in
cerebral flow and perfusion, eventually leading to ischemia and brain infarction.
Increased blood pressure can also make intracranial hemorrhages bleed faster,
also increasing ICP.

Severely raised ICP, if caused by a unilateral space-occupying lesion (e.g. a

hematoma) can result in midline shift, a dangerous sequela in which the brain
 39

moves toward one side as the result of massive swelling in a cerebral

hemisphere. Midline shift can compress the ventricles and lead to
hydrocephalus.[12] Prognosis is much worse in patients with midline shift than in
those without it. Another dire consequence of increased ICP combined with a
space-occupying process is brain herniation (usually uncal or tonsilar). In uncal
herniation, the uncus hippocampus becomes compressed against the free edge of
the tentorium cerebelli, frequently leading to brainstem compression. If
brainstem compression is involved, it may lead to respiratory depression and is
potentially fatal. This herniation is often referred to as "coning".

Major causes of morbidity due to raised intracranial pressure are due to global
brain infarction as well as decreased respiratory drive due to brain herniation.

Stages of intracranial hypertension

Minimal increases in ICP due to compensatory mechanisms is known as stage 1

of intracranial hypertension. When the lesion volume continues to increase
beyond the point of compensation, the ICP has no other resource, but to increase.
Any change in volume greater than 100–120 mL would mean a drastic increase
in ICP. This is stage 2 of intracranial hypertension. Characteristics of stage 2 of
intracranial hypertension include compromise of neuronal oxygenation and
systemic arteriolar vasoconstriction to increase MAP and CPP. Stage 3
intracranial hypertension is characterised by a sustained increased ICP, with
dramatic changes in ICP with small changes in volume. In stage 3, as the ICP
approaches the MAP, it becomes more and more difficult to squeeze blood into
the intracranial space. The body’s response to a decrease in CPP is to raise blood
pressure and dilate blood vessels in the brain. This results in increased cerebral
blood volume, which increases ICP, lowering CPP and perpetuating this vicious
cycle. This results in widespread reduction in cerebral flow and perfusion,
eventually leading to ischemia and brain infarction. Neurologic changes seen in
increased ICP are mostly due to hypoxia and hypercapnea and are as follows:
decreased level of consciousness (LOC), Cheyne-Stokes respirations,
hyperventilation, sluggish dilated pupils and widened pulse pressure.

Causes

Causes of increased intracranial pressure can be classified by the mechanism in

which ICP is increased:

 mass effect such as brain tumor, infarction with edema, contusions,

subdural or epidural hematoma, or abscesses all tend to deform the
adjacent brain.
 generalized brain swelling can occur in ischemic-anoxia states, acute
liver failure, hypertensive encephalopathy, pseudotumor cerebri,
hypercarbia, and Reye hepatocerebral syndrome. These conditions tend
to decrease the cerebral perfusion pressure but with minimal tissue
shifts.
 increase in venous pressure can be due to venous sinus thrombosis,
heart failure, or obstruction of superior mediastinal or jugular veins.
 40

 obstruction to CSF flow and/or absorption can occur in hydrocephalus

(blockage in ventricles or subarachnoid space at base of brain, e.g., by
Arnold-Chiari malformation), extensive meningeal disease (e.g., infection,
carcinoma, granuloma, or hemorrhage), or obstruction in cerebral
convexities and superior sagittal sinus (decreased absorption).

Main article: hydrocephalus

 increased CSF production can occur in meningitis, subarachnoid

hemorrhage, or choroid plexus tumor.
 Idiopathic or unknown cause (idiopathic intracranial hypertension)
 Cerebral venous sinus thrombosis
 Acute liver failure[13]
 craniosynostosis

Signs and symptoms

In general, symptoms and signs that suggest a rise in ICP including headache,
vomiting without nausea, ocular palsies, altered level of consciousness, back pain
and papilledema. If papilledema is protracted, it may lead to visual disturbances,
optic atrophy, and eventually blindness.

In addition to the above, if mass effect is present with resulting displacement of

brain tissue, additional signs may include pupillary dilatation, abducens palsies,
and the Cushing's triad. Cushing's triad involves an increased systolic blood
pressure, a widened pulse pressure, bradycardia, and an abnormal respiratory
pattern.[14] In children, a slow heart rate is especially suggestive of high ICP.

Irregular respirations occur when injury to parts of the brain interfere with the
respiratory drive. Cheyne-Stokes respiration, in which breathing is rapid for a
period and then absent for a period, occurs because of injury to the cerebral
hemispheres or diencephalon.[15] Hyperventilation can occur when the brain
stem or tegmentum is damaged.[15]

As a rule, patients with normal blood pressure retain normal alertness with ICP
of 25–40 mmHg (unless tissue shifts at the same time). Only when ICP exceeds
40–50 mmHg do CPP and cerebral perfusion decrease to a level that results in
loss of consciousness. Any further elevations will lead to brain infarction and
brain death.

In infants and small children, the effects of ICP differ because their cranial
sutures have not closed. In infants, the fontanels, or soft spots on the head where
the skull bones have not yet fused, bulge when ICP gets too high.

A swollen optic nerve is a reliable sign that ICP is elevated.[citation needed]

 41

Treatment

The treatment for IH depends on the etiology. In addition to management of the

underlying causes, major considerations in acute treatment of increased ICP
relates to the management of stroke and cerebral trauma.

A very common treatment for long-term, especially idiopathic, cranial

hypertension is medication with a special diuretic, especially one prescribed by a
neurologist.

In patients who have high ICP due to an acute injury it is particularly important
to ensure adequate airway, breathing, and oxygenation. Inadequate blood
oxygen levels (hypoxia) or excessively high carbon dioxide levels (hypercapnia)
cause cerebral blood vessels to dilate, increasing the flow of blood to the brain
and causing the ICP to rise.[16] Inadequate oxygenation also forces brain cells to
produce energy using anaerobic metabolism, which produces lactic acid and
lowers pH, also dilating blood vessels and exacerbating the problem.[6]
Conversely, blood vessels constrict when carbon dioxide levels are below
normal, so hyperventilating a patient with a ventilator or bag valve mask can
temporarily reduce ICP. Hyperventilation was formerly a part of the standard
treatment of traumatic brain injuries, but the induced constriction of blood
vessels limits blood flow to the brain at a time when the brain may already be
ischemic -- hence it is no longer widely used.[17] Furthermore, the brain adjusts
to the new level of carbon dioxide after 48 to 72 hours of hyperventilation, which
could cause the vessels to rapidly dilate if carbon-dioxide levels were returned to
normal too quickly.[17] Hyperventilation is still used if ICP is resistant to other
methods of control, or there are signs of brain herniation because the damage
herniation can cause is so severe that it may be worthwhile to constrict blood
vessels even if doing so reduces blood flow. ICP can also be lowered by raising
the head of the bed, improving venous drainage. A side effect of this is that it
could lower pressure of blood to the head, resulting in a reduced and possibly
inadequate blood supply to the brain. Venous drainage may also be impeded by
external factors such as hard collars to immobilize the neck in trauma patients,
and this may also increase the ICP. Sandbags may be used to further limit neck
movement.

In the hospital, the blood pressure can be artificially increased in order to

increase CPP, increase perfusion, oxygenate tissues, remove wastes and thereby
lessen swelling.[17] Since hypertension is the body's way of forcing blood into the
brain, medical professionals do not normally interfere with it when it is found in
a patient with a head injury.[15] When it is necessary to decrease cerebral blood
flow, MAP can be lowered using common antihypertensive agents such as
calcium channel blockers.[6] If there is an intact blood–brain barrier,
osmotherapy may be carried out by administering IV mannitol to create a
hypertonic solution within the blood to draw water out of the neurons. This
helps to reduce the fluid within the intracranial space, however prolonged
administration may lead to increase in ICP.[18]
 42

Struggling, restlessness, and seizures can increase metabolic demands and

oxygen consumption, as well as increasing blood pressure.[16][19] Analgesia and
sedation (particularly in the pre-hospital, ER, and intensive care setting) are
used to reduce agitation and metabolic needs of the brain, but these medications
may cause low blood pressure and other side effects.[6] Thus if full sedation alone
is ineffective, patients may be paralyzed with drugs such as atracurium. Paralysis
allows the cerebral veins to drain more easily, but can mask signs of seizures,
and the drugs can have other harmful effects.[16] Paralysing drugs are only
introduced if patients are fully sedated (this is essentially the same as a general
anaesthetic)

Intracranial pressure can be measured continuously with intracranial

transducers. A catheter can be surgically inserted into one of the brain's lateral
ventricles and can be used to drain CSF (cerebrospinal fluid) in order to decrease
ICP's. This type of drain is known as an EVD (extraventricular drain).[6] In rare
situations when only small amounts of CSF are to be drained to reduce ICP's,
drainage of CSF via lumbar puncture can be used as a treatment. There are many
clinical studies of non-invasive intracranial pressure measurement methods
currently being implemented, aimed to find reliable and accurate way to
measure ICP non-invasively. Such method could improve diagnostics of
traumatic brain injury and many other conditions associated with intracranial
hypertension.[citation needed]

Craniotomies are holes drilled in the skull to remove intracranial hematomas or

relieve pressure from parts of the brain.[6] As raised ICP's may be caused by the
presence of a mass, removal of this via craniotomy will decrease raised ICP's.

A drastic treatment for increased ICP is decompressive craniectomy,[20] in which

a part of the skull is removed and the dura mater is expanded to allow the brain
to swell without crushing it or causing herniation.[17] The section of bone
removed, known as a bone flap, can be stored in the patient's abdomen and
resited back to complete the skull once the acute cause of raised ICP's has
resolved. Alternatively a synthetic material may be used to replace the removed
bone section (see cranioplasty)

Low ICP
Main article: Intracranial hypotension

It is also possible for the intracranial pressure to drop below normal levels,
though increased intracranial pressure is a far more common (and far more
serious) sign. The symptoms for both conditions are often the same, leading
many medical experts to believe that it is the change in pressure rather than the
pressure itself causing the above symptoms.

Main article: Cerebrospinal fluid leak

Spontaneous intracranial hypotension may occur as a result of an occult leak of

CSF into another body cavity. More commonly, decreased ICP is the result of
lumbar puncture or other medical procedures involving the brain or spinal cord.
 43

Various medical imaging technologies exist to assist in identifying the cause of

decreased ICP. Often, the syndrome is self-limiting, especially if it is the result of
a medical procedure. If persistent intracranial hypotension is the result of a
lumbar puncture, a "blood patch" may be applied to seal the site of CSF leakage.
Various medical treatments have been proposed; only the intravenous
administration of caffeine and theophylline has shown to be particularly
useful.[21]

Hydrocephalus

Hydrocephalus can be caused by impaired cerebrospinal fluid (CSF) flow, reabsorption, or excessive
CSF production.

 The most common cause of hydrocephalus is CSF flow obstruction, hindering the free passage
of cerebrospinal fluid through the ventricular system and subarachnoid space (e.g., stenosis of
the cerebral aqueduct or obstruction of the interventricular foramina - foramina of Monro
secondary to tumors, hemorrhages, infections or congenital malformations).
 Hydrocephalus can also be caused by overproduction of cerebrospinal fluid (relative
obstruction) (e.g., papilloma of choroid plexus).

Based on its underlying mechanisms, hydrocephalus can be classified into communicating and non-
communicating (obstructive). Both forms can be either congenital or acquired.

Communicating

Communicating hydrocephalus, also known as non-obstructive hydrocephalus, is caused by

impaired cerebrospinal fluid resorption in the absence of any CSF-flow obstruction between the
ventricles and subarachnoid space. It has been theorized that this is due to functional impairment of the
arachnoidal granulations (also called arachnoid granulations or Pacchioni's granulations), which are
located along the superior sagittal sinus and is the site of cerebrospinal fluid resorption back into the
venous system. Various neurologic conditions may result in communicating hydrocephalus, including
subarachnoid/intraventricular hemorrhage, meningitis and congenital absence of arachnoid villi.
Scarring and fibrosis of the subarachnoid space following infectious, inflammatory, or hemorrhagic
events can also prevent resorption of CSF, causing diffuse ventricular dilatation.

 Normal pressure hydrocephalus (NPH) is a particular form of communicating

hydrocephalus, characterized by enlarged cerebral ventricles, with only intermittently
elevated cerebrospinal fluid pressure. The diagnosis of NPH can be established only with the
help of continuous intraventricular pressure recordings (over 24 hours or even longer), since
more often than not instant measurements yield normal pressure values. Dynamic compliance
studies may be also helpful. Altered compliance (elasticity) of the ventricular walls, as well as
increased viscosity of the cerebrospinal fluid, may play a role in the pathogenesis of normal
pressure hydrocephalus.
 Hydrocephalus ex vacuo also refers to an enlargement of cerebral ventricles and
subarachnoid spaces, and is usually due to brain atrophy (as it occurs in dementias), post-
traumatic brain injuries and even in some psychiatric disorders, such as schizophrenia. As
opposed to hydrocephalus, this is a compensatory enlargement of the CSF-spaces in
response to brain parenchyma loss - it is not the result of increased CSF pressure.

Non-communicating

Non-communicating hydrocephalus, or obstructive hydrocephalus, is caused by a CSF-flow

obstruction ultimately preventing CSF from flowing into the subarachnoid space (either due to external
compression or intraventricular mass lesions).
 44

 Foramen of Monro obstruction may lead to dilation of one or, if large enough (e.g., in
Colloid cyst), both lateral ventricles.
 The aqueduct of Sylvius, normally narrow to begin with, may be obstructed by a number of
genetically or acquired lesions (e.g., atresia, ependymitis, hemorrhage, tumor) and lead to
dilation of both lateral ventricles as well as the third ventricle.
 Fourth ventricle obstruction will lead to dilatation of the aqueduct as well as the lateral and
third ventricles (e.g., Chiari malformation).
 The foramina of Luschka and foramen of Magendie may be obstructed due to congenital
failure of opening (e.g., Dandy-Walker malformation).

Congenital

Main articles: Arnold-Chiari malformation and Dandy-Walker malformation

The cranial bones fuse by the end of the third year of life. For head enlargement to occur,
hydrocephalus must occur before then. The causes are usually genetic but can also be acquired and
usually occur within the first few months of life, which include 1) intraventricular matrix hemorrhages
in premature infants, 2) infections, 3) type II Arnold-Chiari malformation, 4) aqueduct atresia and
stenosis, and 5) Dandy-Walker malformation.

In newborns and toddlers with hydrocephalus, the head circumference is enlarged rapidly and soon
surpasses the 97th percentile. Since the skull bones have not yet firmly joined together, bulging, firm
anterior and posterior fontanelles may be present even when the patient is in an upright position.

The infant exhibits fretfulness, poor feeding, and frequent vomiting. As the hydrocephalus progresses,
torpor sets in, and the infant shows lack of interest in his surroundings. Later on, the upper eyelids
become retracted and the eyes are turned downwards (due to hydrocephalic pressure on the
mesencephalic tegmentum and paralysis of upward gaze). Movements become weak and the arms may
become tremulous. Papilledema is absent but there may be reduction of vision. The head becomes so
enlarged that the child may eventually be bedridden.

About 80-90% of fetuses or newborn infants with spina bifida—often associated with meningocele or
myelomeningocele—develop hydrocephalus.[7]

Acquired

This condition is acquired as a consequence of CNS infections, meningitis, brain tumors, head trauma,
intracranial hemorrhage (subarachnoid or intraparenchymal) and is usually extremely painful.

Effects

Because hydrocephalus can injure the brain, thought and behavior may be adversely affected. Learning
disabilities including short-term memory loss are common among those with hydrocephalus, who tend
to score better on verbal IQ than on performance IQ, which is thought to reflect the distribution of
nerve damage to the brain. However the severity of hydrocephalus can differ considerably between
individuals and some are of average or above-average intelligence. Someone with hydrocephalus may
have motion and visual problems, problems with coordination, or may be clumsy. They may reach
puberty earlier than the average child (see precocious puberty). About one in four develops epilepsy.

Treatment

Hydrocephalus treatment is surgical, generally creating various types of cerebral shunts. It involves the
placement of a ventricular catheter (a tube made of silastic), into the cerebral ventricles to bypass the
flow obstruction/malfunctioning arachnoidal granulations and drain the excess fluid into other body
cavities, from where it can be resorbed. Most shunts drain the fluid into the peritoneal cavity
(ventriculo-peritoneal shunt), but alternative sites include the right atrium (ventriculo-atrial shunt),
pleural cavity (ventriculo-pleural shunt), and gallbladder. A shunt system can also be placed in the
 45

lumbar space of the spine and have the CSF redirected to the peritoneal cavity (Lumbar-peritoneal
shunt). An alternative treatment for obstructive hydrocephalus in selected patients is the endoscopic
third ventriculostomy (ETV), whereby a surgically created opening in the floor of the third ventricle
allows the CSF to flow directly to the basal cisterns, thereby shortcutting any obstruction, as in
aqueductal stenosis. This may or may not be appropriate based on individual anatomy.

Shunt complications

Examples of possible complications include shunt malfunction, shunt failure, and shunt infection,
along with infection of the shunt tract following surgery (the most common reason for shunt failure is
infection of the shunt tract). Although a shunt generally works well, it may stop working if it
disconnects, becomes blocked (clogged), infected, or it is outgrown. If this happens the cerebrospinal
fluid will begin to accumulate again and a number of physical symptoms will develop (headaches,
nausea, vomiting, photophobia/light sensitivity), some extremely serious, like seizures. The shunt
failure rate is also relatively high (of the 40,000 surgeries performed annually to treat hydrocephalus,
only 30% are a patient's first surgery)[8] and it is not uncommon for patients to have multiple shunt
revisions within their lifetime.

The diagnosis of cerebrospinal fluid buildup is complex and requires specialist expertise.

Another complication can occur when CSF drains more rapidly than it is produced by the choroid
plexus, causing symptoms -listlessness, severe headaches, irritability, light sensitivity, auditory
hyperesthesia (sound sensitivity), nausea, vomiting, dizziness, vertigo, migraines, seizures, a change in
personality, weakness in the arms or legs, strabismus, and double vision - to appear when the patient is
vertical. If the patient lies down, the symptoms usually vanish in a short amount of time. A CT scan
may or may not show any change in ventricle size, particularly if the patient has a history of slit-like
ventricles. Difficulty in diagnosing overdrainage can make treatment of this complication particularly
frustrating for patients and their families.

Resistance to traditional analgesic pharmacological therapy may also be a sign of shunt overdrainage
or failure. Diagnosis of the particular complication usually depends on when the symptoms appear -
that is, whether symptoms occur when the patient is upright or in a prone position, with the head at
roughly the same level as the feet.