Headache

Question 1

MIGRAINE

Answer 1

Recurrent, severe headache which is usually unilateral and throbbing in nature
May be be associated with aura, nausea and photosensitivity
Aggravated by, or causes avoidance of, routine activities of daily living. Patients often describe ‘going to bed’.
In women may be associated with menstruation

Acute Mx: Triptans are useful in the acute treatment of migraines.
Prophylaxis: Topiramate and propranolol are useful for migraine prophylaxis.

Question 2

TENSION HEADACHE

Answer 2

Recurrent, non-disabling, bilateral headache, often described as a ‘tight-band’
Not aggravated by routine activities of daily living

Mx: This is a classic description of a tension-type headache. The suggested first line treatments are aspirin, paracetamol or NSAIDS. It is not recommended to use opioids in this case.

Question 3

CLUSTER HEADACHE

Answer 3

Pain typical occurs once or twice a day, each episode lasting 15 mins - 2 hours with clusters typically lasting 4-12 weeks
Intense pain around one eye (recurrent attacks ‘always’ affect same side)
Patient is restless during an attack
Accompanied by redness, lacrimation, lid swelling
More common in men and smokers

Mx?

NB: Some neurologists use the term trigeminal autonomic cephalgia to group a number of conditions including cluster headache, paroxysmal hemicrania and short-lived unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). It is recommended such patients are referred for specialist assessment as specific treatment may be required, for example it is known paroxysmal hemicrania responds very well to indomethacin

Question 4

TEMPORAL ARTERITIS

Answer 4

Typically patient > 60 years old
Usually rapid onset (e.g. < 1 month) of unilateral headache
Jaw claudication (65%)
Tender, palpable temporal artery
Raised ESR

Question 5

MEDICATION OVERUSE HEADACHE

Answer 5

Present for 15 days or more per month
Developed or worsened whilst taking regular symptomatic medication
Patients using opioids and triptans are at most risk
May be psychiatric co-morbidity

Question 6

Other Causes of Acute Headache

Answer 6

Acute single episode:

meningitis
encephalitis
subarachnoid haemorrhage
head injury
sinusitis
glaucoma (acute closed-angle)
tropical illness e.g. Malaria

Question 7

Other Causes of Chronic Headache

Answer 7

Chronic headache:

chronically raised ICP
Paget’s disease
psychological

Question 8

THUNDERCLAP HEADACHE

Answer 8

Thunderclap headache describes a sudden (reaches maximum severity within seconds to minutes of onset) and severe headache.

Causes
subarachnoid hemorrhage
cerebral venous sinus thrombosis
internal carotid artery dissection
pituitary apoplexy
reversible cerebral vasoconstriction syndrome
primary sexual headache
posterior reversible leucoencephalopathy syndrome

Question 9

Internal Carotid Artery Dissection: Example Question

Answer 9

A 34 year old man attended the Emergency Department after experiencing a severe sudden onset headache at home. The pain was felt across the whole of the head and reached a 10/10 severity within a few seconds of onset. Since the headache began the patient had experienced a loud pulsatile pounding noise in his right ear. There was no reported loss of consciousness or other neurological symptoms. In the preceding days the patient had been fit and well. On close questioning he recalled that that morning he had been struck hard in the face by a soccer ball while watching his son’s team.

The patient had no significant past medical history and took no medications. There was no family history of neurological disease.

On examination, the patient’s right pupil was constricted compared to his left, with both pupils reactive to light. There was a partial ptosis of the right eye. Cranial nerve examination was otherwise unremarkable except for possible right hypoglossal palsy. Examination of the remainder of the peripheral nervous system was remarkable.

Details of initial investigations are given below.

CT brain (non-contrast): no acute intracranial pathology identified; normal ventricular system; no boney injury.

Lumbar puncture:

CSF red cells	2 / mm³
CSF white cells	4 / mm³
CSF gram stain	unremarkable
CSF glucose	60 % serum level
CSF protein	0.65 g / L
CSF	negative for haemoglobin break down products

What is the correct diagnosis?

Vertebral artery dissection
> Internal carotid artery dissection
Posterior reversible encephalopathy syndrome
Reversible cerebrovascular vasoconstriction syndrome
Posterior communicating artery aneurysm

Internal carotid artery dissection can present with thunderclap headache, commonly following minor trauma, as in this case. Possible associated symptoms and signs include homolateral Horner’s syndrome, tinnitus or tongue palsy. CT brain and lumbar puncture are usually normal (or near normal in the case of LP) with diagnosis confirmed by angiography.

The remaining options are all possible causes of thunderclap headache. Vertebral artery dissection would typically cause a posterior circulation stroke pattern of signs and symptoms. Reversible cerebrovascular vasoconstriction syndrome is associated with hypertension and seizures and diagnosed by arterial beeding on angiography. Posterior reversible encephalopathy syndrome is also associated with hypertension and specific changes on MRI brain secondary to vasogenic brain oedema. Posterior communicating artery aneurysm causes compression of the third nerve with unilateral mydriasis without other signs of third nerve palsy.

Question 10

Cluster Headaches - Features

Answer 10

Cluster headaches* are more common in men (5:1) and smokers.

Features
pain typical occurs once or twice a day, each episode lasting 15 mins - 2 hours
clusters typically last 4-12 weeks
intense pain around one eye (recurrent attacks ‘always’ affect same side)
patient is restless during an attack
accompanied by redness, lacrimation, lid swelling
nasal stuffiness
miosis and ptosis in a minority

*some neurologists use the term trigeminal autonomic cephalgia to group a number of conditions including cluster headache, paroxysmal hemicrania and short-lived unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). It is recommended such patients are referred for specialist assessment as specific treatment may be required, for example it is known paroxysmal hemicrania responds very well to indomethacin

Question 11

Headache - Diagnosis: Example Question

Answer 11

A 32-year-old male presents with his 4th episode of worst ever headache in one week. He describes the headache to always be of sudden onset on the left side of his head, of 10 out of 10 severity and that he finds bright lights extremely distressing during these periods. The episodes last for around 30 minutes, typically after dinner. He also describes redness and swelling of his left eye and a blocked left nostril during the headaches, associated with tearing of his left eye.

He has no past medical history and family history of migraines. He denies illicit drug use, is a non-smoker and drinks two glasses of wine with dinner every night. Over the past 7 days, he has been self-medicating with paracetamol and ibuprofen. On examination, you notice no focal neurology, no meningism and fundoscopy is unremarkable.

What is the most likely diagnosis?

	Subarachnoid haemorrhage
	First presentations of migraine
	SUNCT (short lasting unilateral neuralgiform headache with conjunctival injection or tearing)
	Medication overuse headache
	> Cluster headaches

The main differentials are between cluster headaches and SUNCT, both of which are headache syndromes resulting in severely painful headaches associated with autonomic symptoms. It would be unusual for autonomic symptoms such as conjunctival injection, lacrimation and rhinorrhoea with migraines. Subarachnoid haemorrhage headaches rarely re-occur without disastrous consequences, focal neurology and reduced GCS. Medication overuse headache are normally of onset after a longer period of analgesia use and are more chronic in character without autonomic symptoms.

In distinguishing cluster headaches and SUNCT, the former are more prevalent in younger males below the age of 40 while SUNCT is more common in older patients above the age of 40. Cluster headaches typically onset at night, last from 15 minutes to 3 hours, while SUNCT can occur at any time of day and typically lasts for seconds to minutes. Cluster headaches rarely onset more than 3 times per day while SUNCT has been described in up to 75 times per day. A transient Horners syndrome is typical during a cluster headache but may be lacking in SUNCT. Lastly, cluster headaches are classically, but not always, triggered by alcohol1. The combination of severe nocturnal onset unilateral headache following alcohol in a patient under 40 years old, lasting for 30 minutes, suggest cluster headaches over SUNCT.

Question 12

Cluster Headaches vs SUNCT (short lasting unilateral neuralgiform headache with conjunctival injection or tearing)

Answer 12

In distinguishing cluster headaches and SUNCT, the former are more prevalent in younger males below the age of 40 while SUNCT is more common in older patients above the age of 40. Cluster headaches typically onset at night, last from 15 minutes to 3 hours, while SUNCT can occur at any time of day and typically lasts for seconds to minutes. Cluster headaches rarely onset more than 3 times per day while SUNCT has been described in up to 75 times per day. A transient Horners syndrome is typical during a cluster headache but may be lacking in SUNCT. Lastly, cluster headaches are classically, but not always, triggered by alcohol.

Question 13

Cluster Headache - Mx

Answer 13

Management
acute: 100% oxygen, subcutaneous or a nasal triptan
prophylaxis: verapamil, prednisolone
NICE recommend seeking specialist advice from a neurologist if a patient develops cluster headaches with respect to neuroimaging

Question 14

Trigeminal Autonomic Cephalagias

Answer 14

The trigeminal autonomic cephalalgias should be side-locked (i.e. one side only) and typically but not exclusively in the retroorbital/temporal region. They should include some autonomic parasympathetic feature such as eye-watering, red eye, running nose, a sensation of fullness in the ear, or miosis. These should be ipsilateral to the pain. They are a spectrum and most conveniently differentiated by how long the headache lasts for and how frequent the attacks happen per day. Some features are quite noticeable in TAC, e.g in a cluster headache (aka ‘suicide headaches’) people are usually very animated and pace about/hold their head in pain/want to smash their head against the wall (contrast this to migraine: which is not a TAC and usually involves sitting still in a dark room and not making any noise).

Question 15

Trigeminal Autonomic Cephalagias - International Classification

Answer 15

It is worth looking up the International Classification of Headache Disorders diagnostic criteria for TACs. Here are some important features:

• Cluster headaches: attacks have a frequency between one every other day and 8 per day and last 15-180 minutes.
• Paroxysmal hemicrania: attacks have a frequency above five per day and last 2-30 min. The condition responds absolutely to indomethacin
• Hemicrania continua: a constant form of paroxysmal hemicrania (no headache-free periods). Also responds absolutely to indomethacin.
• Short-lasting unilateral neuralgiform headache attacks (SUNCT/SUNA): could get 20 attacks in a day, each last around 1600 seconds.

Notice the differences between how long each lasts and how many attacks there can be per day. The rest of the features are quite similar to each other between the headaches, so learn the general features of a TAC then memorise how long each should last and its frequency to help you differentiate them.

Question 16

The Trigeminal Autonomic Cephalagias (TACs)

Answer 16

Trigeminal autonomic cephalalgias (TACs)
cluster headache
paroxysmal hemicrania
hemicrania continua
short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome)
short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA)

Question 17

TAC Diagnosis: Example Question

Answer 17

A 44-year-old male presents to your headache clinic with a 6-month history of left-sided daily headaches located in the frontal and retroorbital area. He denies any pain-free periods. The headaches are of moderate 5/10 severity with unpredictable exacerbations of severe pain going up to 9/10 severity. He describes to you what sounds to you like left-sided conjunctival injection and lacrimation often occurring alongside the headaches. Which of the following is most likely to aid you in making a diagnosis?

	a trial of high flow 100% oxygen
	Lumbar puncture
	> a trial of indomethacin
	CT brain
	MRI brain

A headache with absolutely no pain-free periods otherwise described like this (i.e. like a trigeminal autonomic cephalalgia (TAC)) is hemicrania continua.

Hemicrania continua and paroxysmal hemicrania clearly are the two that completely resolve with indomethacin. The history, therefore, helps differentiate which is which. Practically speaking, you bring these patients in, on two separate days, for a trial injection of indomethacin or placebo (water) where patient (and nurse if possible) is blinded to which is which and we see which one of the two days was associated with resolution of headaches at a later date in clinic (give the patient a headache diary to take home with). Note the 100% oxygen trial would be used for cluster headaches, which tends to respond to this.

Question 18

Post-Lumbar Puncture Headache

Answer 18

Headache following lumbar puncture (LP) occurs in approximately one-third of patients. The pathophysiology of is unclear but may relate to a ‘leak’ of CSF following dural puncture. Post-LP headaches are more common in young females with a low body mass index

Typical features
usually develops within 24-48 hours following LP but may occur up to one week later
may last several days
worsens with upright position
improves with recumbent position

Question 19

Post- Lumbar Puncture Headache - Factors which do and do not contribute

Answer 19

FACTORS WHICH MAY CONTRIBUTE:
Increased needle size
Direction of bevel
Not replacing the stylet
Increased number of LP attempts

FACTORS WHICH DO NOT CONTRIBUTE 
Increased volume of CSF removed
Bed rest following procedure
Increased fluid intake post procedure
Opening pressure of CSF
Position of patient

Question 20

Post-Lumbar Puncture Headache - Mx

Answer 20

Management
supportive initially (analgesia, rest)
if pain continues for more than 72 hours then specific treatment is indicated, to prevent subdural haematoma
treatment options include: blood patch, epidural saline and intravenous caffeine

NB: An epidural blood patch is a surgical procedure that uses autologous blood in order to close one or many holes in the dura mater of the spinal cord, usually as a result of a previous lumbar puncture. The procedure can be used to relieve post dural puncture headaches caused by lumbar puncture (spinal tap).

Question 21

Post-Lumbar Puncture Headache - Example Question

Answer 21

A 23 year old female has re-presented 2 days after discharge from the neurology team with a constant diffuse headache, worse on standing than lying down, without neck stiffness or photophobia, but associated with nausea and vomiting. 48 hours ago, she was an inpatient being investigated for intermittent headaches over the past 8 months, typically over the left side of her frontal and temporal regions, of sudden onset during any time of day, associated with double vision, lasting for ‘hours’ at a time. She was experiencing up to 5 episodes a week, with one episode witnessed during her admission, when the senior house officer noted bilateral restriction in vertical eye movements, adduction and unreactive pupils, spontaneously resolving after 3 hours. Her blood tests were unremarkable.

The patient underwent a CT head, demonstrating no intracranial lesions; and a lumbar puncture:

Opening pressure	12.3 cmH2O
WCC	2 /mm³
RBC	50 /mm³
Protein	0.45 g/l
Glucose	4.5 mmol/l (serum 6.7 mmol/l)
Oligoclonal bands	None present

The patient subsequently self-discharged, reporting no immediate headaches, back pain or lower limb paraesthesiae after the lumbar puncture.

During this second admission, she undergoes a MRI head scan, demonstrating significant diffuse meningeal enhancement and bilateral shallow subdural haemorrhages. What is the appropriate treatment?

	> Oral fluids, caffeine and blood patch
	Repeat lumbar puncture
	Intravenous aciclovir
	Intravenous ceftriaxone
	Neurosurgical input

There are two headaches here: the initial presentation appears to be an unusual migranous phenomenon, possibly ophthalmoplegic migraine, while the second is clearly a low-pressure headache. The neurologists would have correct in initially ruling out any other possible causes of oculoparesis with a lumbar puncture but the CSF constituents are fairly unremarkable.

Do not be alarmed by the report of the MRI head: meningeal enhancement, thickening and shallow subdural haematoma are features of low pressure headaches and do not represent meningitis or subdural haematomas regarding neurosurgical drainage. A repeat lumbar puncture would make exacerbate the problem and hence inappropriate. In view of the low-pressure headache occurring soon after a lumbar puncture, encouraging oral fluids, caffeine and a blood patch by the anaesthetists would be most appropriate.

Question 22

Post-Lumbar Puncture Headache - MRI Report

Answer 22

Do not be alarmed by the report of the MRI head: meningeal enhancement, thickening and shallow subdural haematoma are features of low pressure headaches and do not represent meningitis or subdural haematomas regarding neurosurgical drainage.

Question 23

Acephalgic Migraine

Answer 23

Acephalgic migraine is a frequently missed diagnosis of exclusion, where patients experience auras without headache. Up to 38% of migraneurs experience migrane attacks without and with headache, while 4% of migraneurs exclusively experience migraines without headaches

Example Question:
A 61 year old male presenting with his 6th episode of binocular visual loss, which he describes as ‘lights’ and ‘white dots’ over the past 14 months. He denies any limb or facial weakness or sensory loss. He denies headache. He is an active smoker, with a 60 pack year smoking history and has known hypertension on ramipril 5mg OD. Your neurological exam is unremarkable; CT head demonstrates no acute infarct or haemorrhage. MRI head is unmarkable. What is the likely diagnosis?

	Posterior circulation transient ischaemic attacks (TIAs)
	Posterior circulation strokes
	> Acephalgic migraine
	Multiple sclerosis
	Occipital space occupying lesion

The patient gives a strong history of positive visual symptoms such as flashing lights and dots, with no negative such as weakness, sensory loss or visual loss. This would be far more suggestive of a migranous syndrome or primary retinal pathology than cerebrovascular insufficiency, where negative symptoms would be prominent. In addition, a diagnosis of TIA or stroke should be suspicious in any patient with repeated stereotyped, similar symptoms over a long period of time. It is unlikely any patient will present with recurrent multiple TIAs without stroke over a 14 month period.

Question 24

Migraine Without Aura: Diagnostic Criteria

Answer 24

The International Headache Society has produced the following diagnostic criteria for migraine without aura:

Point
A At least 5 attacks fulfilling criteria B-D

B Headache attacks lasting 4-72 hours* (untreated or unsuccessfully treated)

C Headache has at least two of the following characteristics:

1. unilateral location*
2. pulsating quality (i.e., varying with the heartbeat)
3. moderate or severe pain intensity
4. aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs)

D During headache at least one of the following:

1. nausea and/or vomiting*
2. photophobia and photophobia

E Not attributed to another disorder (history and examination do not suggest a secondary headache disorder or, if they do, it is ruled out by appropriate investigations or headache attacks do not occur for the first time in close temporal relation to the other disorder)

*In children, attacks may be shorter-lasting, headache is more commonly bilateral, and gastrointestinal disturbance is more prominent.

Question 25

Migraine With Aura: Diagnosis

Answer 25

Migraine with aura (seen in around 25% of migraine patients) tends to be easier to diagnose with a typical aura being progressive in nature and may occur hours prior to the headache.
Typical aura include a transient hemianopic disturbance or a spreading scintillating scotoma (‘jagged crescent’). Sensory symptoms may also occur
Visual disturbance usually in BOTH eyes (1 eye is not typical of migraine aura)

If we compare these guidelines to the NICE criteria the following points are noted:
NICE suggests migraines may be unilateral or bilateral
NICE also give more detail about typical auras:

Auras may occur with or without headache and:
are fully reversible
develop over at least 5 minutes
last 5-60 minutes

The following aura symptoms are atypical and may prompt further investigation/referral;
motor weakness
double vision
visual symptoms affecting only one eye
poor balance
decreased level of consciousness.

Question 26

Trigeminal Neuralgia

Answer 26

Trigeminal neuralgia is a pain syndrome characterised by severe unilateral pain. The vast majority of cases are idiopathic but compression of the trigeminal roots by tumours or vascular problems may occur

The International Headache Society defines trigeminal neuralgia as:

• a unilateral disorder characterised by brief electric shock-like pains, abrupt in onset and termination, limited to one or more divisions of the trigeminal nerve
• the pain is commonly evoked by light touch, including washing, shaving, smoking, talking, and brushing the teeth (trigger factors), and frequently occurs spontaneously
• small areas in the nasolabial fold or chin may be particularly susceptible to the precipitation of pain (trigger areas)
• the pains usually remit for variable periods

Question 27

Trigeminal Neuralgia - Mx

Answer 27

Management
carbamazepine is first-line
failure to respond to treatment or atypical features (e.g. < 50 years old) should prompt referral to neurology

Question 28

Trigeminal Neuralgia - Neurosurgery: Example Question

Answer 28

A 65-year-old man attends neurology clinic for review of his long-standing trigeminal neuralgia. He had first experienced symptoms five years previously and been troubled by his illness ever since despite frequent neurology review. The patient experiences attacks of severe shooting pain affecting the right side of his lower face, each episode usually lasting about one hour. The interval between attacks has steadily reduced over the years so that at the present time the patient experiences four to five episodes per week. The patient describes that his symptoms are profoundly limiting his life and that he rarely leaves his house for fear of an attack.

Four years previously, treatment with carbamazepine had been introduced with an initially good response to symptoms. However, patient proved to be intolerant of carbamazepine due to drowsiness. Subsequent trials of treatment with oxcarbazepine, lamotrigine and baclofen had not given lasting relief.

The patient had recently been diagnosed with depression and initiated on treatment with sertraline. He was also suffered from type 2 diabetes currently managed with diet and metformin 500 mg TDS. The patient lived with his wife and had been unable to work as a school-teacher for the past two years due to his symptoms.

Having previously been reluctant to consider surgical intervention, the patient now felt he would be willing to try any options that could improve his symptoms.

MRI brain with / without contrast: sinuses unremarkable without evidence of inflammation; no space occupying lesion; no extra-cranial mass along course of trigeminal nerves; no evidence of widespread demyelination plaque; no evidence of previous infarction; no abnormal enhancement of the trigeminal nerves.

What is the appropriate surgical intervention for this patient?

	Stereotactic radiosurgery
	Balloon compression
	> Microvascular decompression
	Radiofrequency lesioning
	Glycerol rhizolysis

The patient has long-standing and severe trigeminal neuralgia with life-limiting symptoms despite appropriate medical treatment. Surgical intervention should therefore be considered.

In around 95 % of cases, trigeminal neuralgia is believed to be caused by compression of the trigeminal nerve by adjacent blood vessels, although the exact mechanism of the pathophysiology is incompletely understood. In a minority of cases, trigeminal neuralgia can be due to an alternative diagnosis such as sinusitis, extra-cranial or intra-cranial masses, multiple sclerosis or infarction of the thalamus or brainstem.

The MRI brain undergone by the patient does not provide evidence for any of the rare causes of trigeminal neuralgia with the patient’s symptoms therefore very likely due to vascular compression. Using specialist techniques not included in the standard protocol, MRI can detect vascular contact with the trigeminal nerve. However, vascular contact with cranial nerves is also a normal variant in some individuals so these techniques are not routinely used.

Microvascular decompression is therefore the surgical technique of choice and is effective treatment in 95 % of such cases of trigeminal neuralgia. The other possible answers refer to methods of palliative destruction of the trigeminal nerve root, therefore carrying the risk of causing facial numbness. However, they are effective in the minority of trigeminal neuralgia cases not caused by vascular compression.

Question 29

Trigeminal Autonomic Cephalgia - Example Question

Answer 29

A 26 year old female presents with a 4 month history of continuous left sided facial pain and fronto-temporal headache. She reports it to be constantly present and throbbing in nature, with exacerbations of worsened severity every 3 days. She reports exacerbations to typically be associated with injected left eye and left nasal congestion, with occasional teariness in her left eye.

She has no past medical history or drug history except the oral contraceptive pill. Her routine blood tests are unremarkable. A MRI head organised by her GP also demonstrated no intracranial pathology. An trial indomethacin you have organised is positive.

What is the most likely diagnosis?

	Short-lasting unilateral neuralgiform attacks with conjunctival injection and tearing (SUNCT)
	> Hemicrania continua
	Cluster headaches
	Paroxysmal hemicrania
	Migraines

The patient has a constant headache with exacerbations in the distribution of the left ophthalmic distribution of the fifth cranial nerve associated with autonomic symptoms: this represents one of the trigeminal autonomic cephalgias (TACs). TACs is a class of disorders differentiated by the frequency and duration of attacks, and their response to indomethacin.

SUNCT, paroxysmal hemicrania and cluster headaches present with attacks of approximate duration seconds, minutes to 30 minutes, up to 180 minutes respectively. Symptoms are not present in between attacks. Cluster headaches appear more commonly in men while young women are more predisposed to paroxysmal hemicrania. Hemicrania continua produces pain that is always present with exacerbations in severity. Crucially for diagnosis, only hemicrania continua and paroxysmal hemicrania are responsive to indomethacin, making it a useful diagnostic and therapeutic prophylactic drug.

Question 30

Migraine - Example Question

Answer 30

A 25-year-old man presents for review. For the past year, he has been experiencing headaches. These are now occurring around 5-6 times per month and typically ‘last all day’ when they occur. They are not associated with any form of aura. A typical headache is described as a severe throbbing on both sides of his head associated with nausea and lethargy. When he gets such a headache he typically goes to bed so he can ‘sleep it off’. Before going to bed he typically takes one of his father’s diclofenac tablets which seem to help.

Neurological examination is unremarkable.

What is the most likely diagnosis?

	> Migraine
	Cluster headache
	Medication-overuse headache
	Tension headache
	Raised intracranial pressure

This headache is very likely to represent a migraine. Much of the history if very typical, except that the majority of patients usually have unilateral symptoms.

There is no evidence of the kind of medication overuse that can result in regular headaches.

Question 31

Trigeminal Neuralgia - Alternative Diagnosis Ix: Example Question

Answer 31

You see a 46 year-old man who has been referred by his GP to the neurology clinic.

He gives a one year history of facial pain. The pain particularly comes on when he is shaving or brushing his teeth, and he describes it as ‘stabbing’ through the teeth of his upper jaw and over the left side of his face. He has seen a succession of dentists and had several teeth removed, with no relief. The pain has been getting progressively worse, and whereas before it occurred in discrete attacks, it now occurs almost all the time. He has read several online sources and has become convinced that he has a brain tumour, which has led to him becoming depressed and withdrawn.

His past medical history includes essential hypertension, for which he takes perindopril. He also suffers from sinusitis, and has had a sinus washout on more than one occasion. Two years ago whilst on a business trip abroad he had a problem with the vision in his right eye, which spontaneously resolved over a few weeks, and for which he sought no treatment.

General examination is unremarkable. Cranial nerve examination is largely normal but you notice that there is a patch of numbness over the left cheek. Power is 5/5 across all muscle groups in the limbs, reflexes are normal, and plantars are downgoing. Sensation is the limbs is normal.

What is the most appropriate course of action?

Reassure him he has trigeminal neuralgia, for which unfortunately there is no treatment
Reassure him he has trigeminal neuralgia, and start carbamazepine 300mg daily
Refer to the neurosurgeons for microvascular decompression
> Perform MR head with gadolinium contrast
Perform CT head with contrast

This man needs investigation before any further management is considered. He has pain which is typical for trigeminal neuralgia. However, objective sensory loss does not occur in idiopathic trigeminal neuralgia and is highly suggestive of an underlying cause. This may occur due to compression of the trigeminal nerve by a space-occupying lesion such a tumour, or by a demyelinating plaque of multiple sclerosis affecting the trigeminal root at the pons. The episode of transient unilateral visual disturbance that this man suffered two years ago raises the possibility of optic neuritis, and thus the history is suspicious for MS. Malignancy is also a distinct possibility. Gadolinium-enhanced MR of the head is the best investigation to detect both.

Carbamazepine is an effective treatment for trigeminal neuralgia and produces at least some response in 70% of patients. Neurosurgical options such as microvascular decompression are considered only once medical options have been exhausted.

Question 32

Temporal Arteritis

Answer 32

Temporal arteritis

Temporal arteritis is large vessel vasculitis which overlaps with polymyalgia rheumatica (PMR). Histology shows changes which characteristically ‘skips’ certain sections of affected artery whilst damaging others.

Features
typically patient > 60 years old
usually rapid onset (e.g. < 1 month)
headache (found in 85%)
jaw claudication (65%)
visual disturbances secondary to anterior ischemic optic neuropathy
tender, palpable temporal artery
features of PMR: aching, morning stiffness in proximal limb muscles (not weakness)
also lethargy, depression, low-grade fever, anorexia, night sweats

Investigations
raised inflammatory markers: ESR > 50 mm/hr (note ESR < 30 in 10% of patients). CRP may also be elevated
temporal artery biopsy: skip lesions may be present
note creatine kinase and EMG normal

Treatment
high-dose prednisolone - there should be a dramatic response, if not the diagnosis should be reconsidered
urgent ophthalmology review. Patients with visual symptoms should be seen the same-day by an ophthalmologist. Visual damage is often irreversible

Question 33

Medication Overuse Headache

Answer 33

Medication overuse headache is one of the most common causes of chronic daily headache. It may affect up to 1 in 50 people

Features
present for 15 days or more per month
developed or worsened whilst taking regular symptomatic medication
patients using opioids and triptans are at most risk
may be psychiatric co-morbidity

Management (from 2008 SIGN guidelines)
simple analgesics and triptans should be withdrawn abruptly (may initially worsen headaches)
opioid analgesics should be gradually withdrawn

Example Question:

A 32-year-old woman presents to clinic with a constant headache. She has attempted to control this by taking daily paracetamol, ibuprofen and codeine for the last two months. Her headache has not improved. She describes the headache as present almost every single day but is not disabling. There is a concern that she may have a medication overuse headache. What is the most appropriate management?

	Wean off codeine
	Stop codeine abruptly
	Stop codeine and ibuprofen abruptly
	Wean off codeine and ibuprofen
	> Stop all medications abruptly

The correct answer is to stop all medications abruptly. The duration of the headache and regular use of codeine makes the diagnosis of medication overuse headache most likely. Whilst codeine and triptans are most commonly the cause, another analgesia can contribute and all of the analgesia should be stopped abruptly. Likely improvement will be seen within a few days.

Question 34

Thunderclap Headache

Answer 34

Thunderclap headache describes a sudden (reaches maximum severity within seconds to minutes of onset) and severe headache.

Causes
subarachnoid hemorrhage
cerebral venous sinus thrombosis
internal carotid artery dissection
pituitary apoplexy
reversible cerebral vasoconstriction syndrome
primary sexual headache
posterior reversible leucoencephalopathy syndrome

Question 35

Thunderclap Headache: Posterior Reversible Leucoencephalopathy Syndrome - Example Question

Answer 35

A 64 year old man presented to the Emergency Department after becoming unwell at home. His wife reported that the patient experienced a sudden onset and severe headache while watching television. Shortly afterwards she found him to have become confused and drowsy and an ambulance was called. On arrival in the Emergency Department, the patient suffered a witnessed tonic-clonic seizure, self-terminating after two minutes.

The patient had known hypertension and hypercholesterolaemia and had suffered a non-ST elevation myocardial infarction two years before, treated with a drug-eluting stent to the left anterior descending artery. Regular medications included ramipril 10 mg OD, bisoprolol 10 mg OD, bendroflumethiazide 2.5 mg OD, simvastatin 40 mg OD and aspirin 75 mg OD. The patient’s wife reported that compliance with anti-hypertensive medications had been inconsistent and that controlling the patient’s blood pressure had been an on-going problem over the previous two years. The patient was a retired builder and ex-smoker.

On examination, the patient was drowsy (GCS M4V2E3) but was protecting his own airway. Pupils were equal and reactive. The patient was spontaneously moving all his limbs and had downgoing plantar reflexes. Cardiovascular, respiratory and abdominal examination was unremarkable. Initial observations and investigations are listed below.

Blood pressure 220 / 115 mmHg
Heart rate 89 beat / minute
O2 sats (15 L O2) 100 %
Respiratory rate 19 / minute
Temperature 37.1ºC. 

CT brain: no extra-axial bleeding or collection; no intracerebral haemorrhage; no evidence acute ischaemic stroke; no subarachnoid blood; normal ventricular system; mild small vessel disease in keeping with patient’s age.

Lumbar puncture:

CSF red cells	3/ mm³
CSF white cells	3 / mm³
CSF gram stain	unremarkable
CSF glucose	60 % serum level
protein	0.5 g / L
CSF	negative for bilirubin and xanthochromia

Given persistent reduced GCS and need to obtain blood pressure control, patient was intubated and transferred to the neuro intensive care unit. Following discussion with neurological team further imaging was arranged

MR brain with angiography: structurally normal brain as per previous study; bilateral symmetric vasogenic oedema involving the subcortical white matter in the parietal-occipital, posterior temporal and posterior frontal lobes; MRA unremarkable without any area of stenosis or vasospasm.

What is the correct diagnosis?

Reversible cerebral vasoconstriction syndrome
> Posterior reversible leucoencephalopathy syndrome
Acute disseminated encephalomyelitis
Cerebral venous thrombosis
Pituitary apoplexy

Posterior reversible leucoencephalopathy syndrome may present with thunderclap headache, usually followed rapidly by confusion, seizures and visual symptoms. CT brain and lumbar puncture results are usually normal or near normal. The most common causes of PRES are hypertensive encephalopathy (as in this case) and eclampsia. Hypertension is commonly observed. Diagnosis is made by evidence of vasogenic brain oedema on MRI brain. PRES is often associated with reversible cerebrovascular vasoconstriction syndrome with vasospasms on angiography (although not in this case). Acute disseminated encephalomyelitis does not present with thunderclap headache.

Cerebral sinus thrombosis and pituitary apoplexy can both present with thunderclap headache and normal CT brain and LP although the other results and clinical picture in this case are not consistent with these diagnoses. Acute disseminated encephalomyelitis does not present with thunderclap headache.

Question 36

Temporal Arteritis - Example Question

Answer 36

A 60-year-old man presents with a few hours history of severe left sided headache, described as a sharp pain behind the eye and around the temple. When his scalp is touched it elicits severe pain. He describes a transient loss of vision in the left eye that lasted for seconds during the onset of the pain. He has been feeling unwell with fevers and intermittent headaches for the past week. 2 years ago he had been diagnosed with cluster headaches and has had them intermittently, the last attack was 3 months ago.

On examination his scalp was tender to touch, and a prominent temporal artery could be felt. The temperature was 37.9ºC, heart rate 90bpm, respiratory rate 22 breaths per minute, saturating 100% on air. Pupils were equal and reactive to light, no photophobia. no diplopia or ophthalmoplegia on eye movements. Rest of cranial nerve examination was normal. Fundoscopy revealed no evidence of papilloedema.

Na+	137mmol/l
K+	4.3 mmol/l
Urea	5.7 mmol/l
Creatinine	67 µmol/l
Serum glucose	5.8 mmol/l
C Reactive protein (CRP)	78mg/l
Erythrocyte Sedimentation Rate (ESR)	Awaiting results.
Haemoglobin	156 g/l
White cell count	10.2 x 109/L
INR	1.0

What is the next appropriate management step?

	CT Head scan
	Intravenous normal saline
	15L oxygen via a non re-breather mask
	> Prednisolone 60mg orally
	200mg Ibuprofen

This patient has presented with symptoms and signs suggestive of temporal arteritis. Temporal arteritis is a systemic immune-mediated vasculitis affecting medium and large-sized arteries. It typically presents with temporal headache, myalgia, malaise or fever. Symptoms can be subtle. Other features include jaw claudication, diplopia. On examination, there may be scalp tenderness, prominent, beaded or tender temporal arteritis, fever and bruits heard over the carotid, axillary arteries may be present. The history of cluster headaches is a red herring.

CRP can be elevated, even in the presence of a normal ESR. A normal ESR does not exclude the diagnosis. Therefore in this case the next most appropriate management step would be to give high dose steroids (40mg prednisolone, unless the patient has ischaemic, claudication or visual symptoms - give 60mg prednisolone daily instead). Low dose aspirin 75mg daily should be started unless there are contra indications.

A CT scan is not indicated at this point. Oxygen is used in the treatment of cluster headaches.

Question 37

Trigeminal Autonomic Cephalgia - Example Question

Answer 37

A 28 year old female is referred to general medical clinic for review. She has a one year history of very severe right sided headaches. These are associated with eyelid swelling and lacrimation and never occur on the left. Paroxysms last around 2 minutes at a time and attacks occur upwards of 10 times per day. Attacks tend to occur every day for a week or two with a moth or so between attacks. She describes no nausea or vomiting associated with her headaches.

What treatment should you offer?

	Low dose carbamazepine
	> Trial of indomethacin
	Verapamil
	Topirimate
	Prednisolone

The history given above is one of severe, paroxysmal, unilateral headaches with associated autonomic features. The two most likely diagnoses would be cluster headache or paroxysmal hemicrania (PH), with the latter being more likely. It would be unusual for cluster headache attacks to last for less than 5 minutes and a daily frequency of greater than 10 is unusual for cluster headache but not PH. In addition, cluster headaches have a male predilection but PH tends to affect females. 
Paroxysmal hemicrania (or chronic paroxysmal hemicrania if attacks occur for over one year) tends to be highly responsive to treatment with indomethacin, so much so that a trial of this may be considered a diagnostic strategy. 

Low dose carbamazepine is the treatment of choice for trigeminal neuralgia. Verapamil is first line for prophylaxis of cluster headaches. Topiramate may be used in migraine prophylaxis and oral steroids have been used to prevent cluster headaches but have little evidence to support their use.

It may be argued that due to the relative rarity of PH compared with cluster headaches that even with the history above the former may be more likely, however due to the diagnostic response to indomethacin seen in PH it would be appropriate to trial this first.

Question 38

Post-Lumbar Puncture Headache - Diagnosis: Example Question

Answer 38

A 53-year-old lady was admitted to the medical admission unit having presented to the Emergency Department with a severe headache which had developed over the last five days. She described the headache as a continual dull pain across the front of her head and was significantly worsened when she sat up as well as when she coughed or strained. It was alleviated only when she lied down in a dark room; paracetamol 1g QDS and ibuprofen 400mg TDS did not provide any relief. She denied the presence of nausea or vomiting, her vision was not affected and other than feeling tired she did not complain of any other symptoms. Her past medical history was comprised of non-classical migraines and hypothyroidism for which she was prescribed levothyroxine 175mcg OD. Seven days ago she was admitted with a headache, fever and photophobia; review of her medical notes revealed the following results from the previous admission:

Hb 142 g/l
Platelets 326 * 109/l
WBC 11.2 * 109/l

Glucose	5.4 mmol/l
ESR	32 mm/hr
CRP	46 mg/l
PTT	12.2 (NR 12-14s)
APTT	44s (NR 300-46s)
Fibrinogen	5.2 (NR 2-4 g/l)

Urine MCS: NAD
Blood MCS: NAD

CT Head: normal intracranial appearances; no space occupying lesion or haemorrhage identified

Lumbar puncture:

Protein	0.3g (NR 0.2-0.4 g/L)
Glucose	3.6 mmol/l
WCC	8 (<5/mm3)
Opening pressure	15 (NR 10-20 cmH2O)
MCS	NAD

Examination revealed the presence of a female in a dark room lying flat. Her temperature was 36.6ºC, heart rate 77bpm, respiratory rate 16/min and blood pressure 136/78 mmHg. Examination her cardiovascular and respiratory systems were unremarkable. Examination of her neurological system revealed the presence of normal functioning cranial nerves 2-12 with unremarkable fundoscopy; there was no neck stiffness or photophobia objectively. There was no neck stiffness and Kernig’s sign was negative. Examination of her peripheral neurological system was unremarkable.

What is the single next best management option?

	Organise urgent cranial MR venogram scan
	Organise urgent cranial MRI scan
	Commence therapy with sumatriptan
	> Administer epidural blood patch
	Send CSF for xanthochromia analysis

This lady has developed post-lumbar puncture headache (PLPH), a common complication of a lumbar puncture and is thought to be caused by excess leakage of cerebrovascular fluid causing a relatively low intracranial pressure and is aggravated significantly when assuming a non-supine posture. There are of course many other diagnoses that need to be considered, including meningitis, migraine, cortical vein thrombosis, intracerebral haemorrhage and cluster headaches. In most instances however the diagnosis of PLPH can be made clinically. Patients frequently believe the cause of their headaches is due to migraine and therefore report that avoiding bright light alleviates their headache when in fact it is lying down which is alleviating the headache. Management is conservative, including administering analgesia and sufficient fluids. If this fails to resolve the headache the gold standard management is an epidural blood patch.

Question 39

Migraine - Acute vs Preventative Mx

Answer 39

Acute Mx = 5-HT RECEPTOR AGONISTS (eg Sumatriptan)

Preventative Mx = 5-HT RECEPTOR ANTAGONIST

Question 40

Trigeminal Neuralgia - Example Question

Answer 40

A 59-year-old woman is referred by her GP to neurology clinic for assessment. The patient describes intermittent episodes of pain affecting the left side of her face. She recalls the first attack vividly as a sudden onset of severe ‘electric-shock’ pain coming on suddenly around one year previously as she had cleaned her teeth with her electric toothbrush. The pain was felt around the cheek extending down to the jaw-line. The first attack had lasted several hours and she had ultimately attended her dentist and received a filling to a left molar tooth. While symptoms from that episode had resolved, she had then suffered from similar episodes at increasing frequency, approximately every fortnight over the last couple of months. These attacks had on occasion been unprovoked but were sometimes induced by stimulation of the affected area or cold winds. The patient was tearful as she recounted the negative impact her symptoms had had one her lifestyle. There was no history of headaches, sinus symptoms or seizures.

The patient had a fairly unremarkable past-medical history, notable only for hypothyroidism and long-standing struggles to avoid overweight. Her only regular medication was thyroxine 125 micrograms daily and the patient reported no allergies. There was no family history of neurological disease. The patient worked as a law clerk and did not smoke or drink significant alcohol.

Examination demonstrated an unremarkable cranial nerve and peripheral nerve examinations. In particular, colour vision, visual acuity and hearing where normal.

What is the correct first line management of the patients symptoms?

	Gabapentin
	> Carbamazepine
	Pregabalin
	Baclofen
	Lamotrigine

The patient reports a classical history of trigeminal neuralgia. Notable features are the memorable first occurrence, attacks precipitated by touch or vibration and the history of inappropriate dental treatment. Time between attacks often gradually reduces leaving patients quality of life significantly impaired.

The patient has no other symptoms or neurological signs that might suggest an alternative diagnosis such as multiple sclerosis, sinusitis or a space-occupying lesion. In the presence of such features, an MRI brain is the most appropriate investigation.

Carbamazepine is the only drug licensed specifically for trigeminal neuralgia in the UK. In 70 % of patients it provides initial 100 % pain relief. However, caution must be used due to side-effects and drug interactions. Oxcarbazepine is a derivative of carbamazepine with similar efficacy but improved tolerability and side-effect profile.

In the evidence of allergy or intolerance to the above drugs then use of baclofen or lamotrigine should be considered, however the evidence base for both is thin. Gabapentin in combination with ropivacaine injections did show benefit in one randomised controlled trial but this result has not been replicated in subsequent investigations. Pregabalin had reported effectiveness in one prospective study of 53 patients.

Question 41

Headache - Idiopathic Intracranial Hypertension: Example Question

Answer 41

A 25-year-old woman presents to the neurology outpatient clinic with a month history of worsening headache.

The headache is mostly frontal in nature but does move to the back of her head sometimes. It never goes away but is worst in the morning. It is throbbing in nature. In the last week it has begun to make her feel sick, although she has not vomited. She has also developed a thudding sound in her ears which she first noticed when trying to go to sleep at night but now sometimes hears at other times. She has no change in her vision or photophobia.

She has no past medical history of note and has no allergies. Her only current medication is the oral contraceptive pill. She is obese, drinks no alcohol and smokes ten cigarettes per day.

On examination her heart rate is 90/min and her blood pressure is 165/94 mmHg.
Her pupils are equal and reactive and her visual fields are full to confrontation. Vision is 6/6 in both eyes and extra-ocular movements are normal. Fundoscopy reveals slight blurring of the optic disc margins with a normal retina.

Examination of the other cranial nerves reveals no deficits. On examination of the upper and lower limbs, tone, power, coordination and reflexes are all normal, with downgoing planters. Her BMI is 31.

Blood tests:

Hb 150 g/l
Platelets 250 * 109/l
WBC 7 * 109/l

Na+ 136 mmol/l
K+ 4 mmol/l
Urea 6 mmol/l
Creatinine 72 µmol/l

What is the next most appropriate imaging investigation?

	CT angiogram head
	CT head without contrast
	MR angiogram head
	MRI head without contrast
	> MR venogram head

This lady has headache, worse on laying down, associated with nausea, pulsating tinnitus and papilloedema. These symptoms are suggestive of raised intracranial pressure and idiopathic intracranial hypertension. She is high risk for this condition given her young age, obesity and use of the oral contraceptive pill.

The diagnosis is supported by her lack of localising neurology. She does not yet have signs of visual impairment.

Formal diagnosis (by Modified Dandy criteria), requires CSF opening pressure greater than 25 cmH2O and normal brain imaging. Imaging is required to exclude venous sinus thrombosis, which could result in the same signs and symptoms and is also more common in women on the oral contraceptive pill. The gold standard imaging for this would be MRI with contrast of the head and orbits and MR venogram

Question 42

Guidelines on Cluster Headache Diagnosis

Answer 42

NICE guidelines characterise cluster headaches as one-sided headache in or around the eye or temporal region associated with signs of autonomic dysfunction on the same side.

Attacks of pain:
Usually last for 15-180 minutes
Almost always described as the most severe pain known
Tend to recur at the same time each day
Often wake the person shortly after falling asleep

Signs of symptoms of autonomic dysfunction include:
Rhinorrhoea or nasal congestion
Red eye and/or lacrimation
Facial or forehead sweating or flushing
Constriction of the pupil and/or ptosis
Eyelid oedema
A sense of aural fullness

Question 43

Cluster Headache vs Paroxysmal Hemcrania - Example Question

Answer 43

You have been referred a 45-year-old man by the Accident and Emergency doctors with a severe headache. The headache woke him up at 3am, and he describes it as the worst headache he’s ever had, (although he admits he’s not a regular headache sufferer). He has had seven episodes like this over the past two weeks that have followed a very similar pattern, with the other two headaches lasting around 60 minutes before going. The pain is mainly around the left eye and temple and is sharp in nature. You have to ask him to sit down to examine him because he is up and pacing around his room, clearly very agitated. On examining him you note that his left eye is watering and swollen, and there’s some redness and mild bruising just above the eye. When you ask him about this bruising he says that the pain was so bad he bashed his head against the fridge door to try and help take it away.

On examination he has normal power, sensation and reflexes in all four limbs.

On examining his cranial nerves you notice that he has a mild left sided ptosis and miosis, and there is conjunctival injection and lacrimation on that side too.

His neck movements are slow but complete, and he has no obvious stiffness or photophobia

What is the most likely cause of his headache?

	> Cluster headache
	Subarachnoid haemorrhage
	Paroxysmal hemicrania
	Migraine
	Tension headache

What is described above is the classical cluster headache. NICE guidelines characterise cluster headaches as one-sided headache in or around the eye or temporal region associated with signs of autonomic dysfunction on the same side.

Attacks of pain:
Usually last for 15-180 minutes
Almost always described as the most severe pain known
Tend to recur at the same time each day
Often wake the person shortly after falling asleep

Signs of symptoms of autonomic dysfunction include:
Rhinorrhoea or nasal congestion
Red eye and/or lacrimation
Facial or forehead sweating or flushing
Constriction of the pupil and/or ptosis
Eyelid oedema
A sense of aural fullness

Tension headaches tend to be bilateral, pressing, with a pain intensity of mild to moderate and without other associated signs or symptoms.

Migraines can be both unilateral or bilateral and tend to be throbbing or banging in nature. While they can be severe in nature, they tend not to be described as the worst pain the patient has ever had. Unlike the agitation that comes with cluster headaches, patients with migraines tend to avoid activities of daily living shutting themselves in quiet dark rooms to provide relief. In addition the headaches tend to be longer, most commonly being between 4 hours and 3 days in adults.

Paroxysmal hemicrania attacks then to be much shorter (2-30 minutes), happen with much higher frequency (>5 times/day), and are more common in women. In an exam situation they will also tend to mention that the patient has found complete relief with indometacin (or this will be the subject of the question).

Subarachnoid haemorrhage headaches do not have a preceding history of previous attacks.

Question 44

MIGRAINE - Mx Acute vs Prophylaxis

Answer 44

It should be noted that as a general rule 5-HT receptor agonists are used in the acute treatment of migraine whilst 5-HT receptor antagonists are used in prophylaxis. NICE produced guidelines in 2012 on the management of headache, including migraines.

Question 45

MIGRAINE - Acute Mx

Answer 45

Acute treatment
- first-line: offer combination therapy with an oral triptan and an NSAID, or an oral triptan and paracetamol
- for young people aged 12-17 years consider a nasal triptan in preference to an oral triptan
if the above measures are not effective or not tolerated offer a non-oral preparation of metoclopramide* or prochlorperazine and consider adding a non-oral NSAID or triptan

*caution should be exercised with young patients as acute dystonic reactions may develop

Question 46

MIGRAINE - Prophylaxis

Answer 46

Prophylaxis
prophylaxis should be given if patients are experiencing 2 or more attacks per month. Modern treatment is effective in about 60% of patients.
NICE advise either topiramate or propranolol ‘according to the person’s preference, comorbidities and risk of adverse events’. Propranolol should be used in preference to topiramate in women of child bearing age as it may be teratogenic and it can reduce the effectiveness of hormonal contraceptives
if these measures fail NICE recommend ‘a course of up to 10 sessions of acupuncture over 5-8 weeks’ or gabapentin
NICE recommend: ‘Advise people with migraine that riboflavin (400 mg once a day) may be effective in reducing migraine frequency and intensity for some people’
for women with predictable menstrual migraine treatment NICE recommend either frovatriptan (2.5 mg twice a day) or zolmitriptan (2.5 mg twice or three times a day) as a type of ‘mini-prophylaxis’
pizotifen is no longer recommend. Adverse effects such as weight gain & drowsiness are common

Question 47

Episodic Cluster Headache Prophylaxis - Example Question

Answer 47

A 32 year-old accountant presents to the neurology clinic.

For the last year he has been troubled by severe headaches. These occur in the morning, sometimes waking him from sleep. There is a sudden onset of stabbing pain behind the left eye, at the onset of which he feels the need to pace around the room, pounding his head in an effort to ease the pain. During the attacks his left eye is watery and his nose his congested. On more than one occasion he has noticed that his right pupil appears enlarged during the attacks. He tells you very clearly that the pain is so severe that at times during the attacks he has considered jumping out of the top floor of the office building where he works. Each attack lasts one or two hours, and between the attacks he feels fine.

He shows you a detailed headache dairy in which he has documented every attack over the last year. For example, in January he had a period of nine days in which attacks occurred several times daily, but in February and March he was headache free. During April he developed severe headaches which occurred almost every day until June. He then had another period of relief until August, and so on.

He has no other past medical history and no allergies.

Examination is unremarkable.

What is the best treatment for prophylaxis of this man’s headaches?

	100% oxygen
	> Verapamil
	Sumatriptan
	Propranolol
	Lithium

This is a classic description of episodic cluster headache.

Interestingly, the patient mentioned that his right pupil was enlarged, but most likely he is describing ipsilateral Horner’s syndrome, which may occur during cluster attacks.

Verapamil is the established first-line agent for the prophylaxis of episodic and chronic cluster headache.

100% oxygen is the first-line treatment for acute attacks of cluster headache.

Sumatriptan is commonly used for acute attacks of cluster headache and migraine, often subcutaneously.

Propranolol is a first-line drug for the prophylaxis of migraine.

Lithium is a second-line agent for the prophylaxis of cluster headache.

Question 48

CLUSTER HEADACHE - In Brief

Answer 48

NICE guidelines suggest that one should diagnose a cluster headache if:
Pain lasts 15 minutes to 3 hours and is associated with intense restlessness and agitation.
Episodes occur with a frequency between one every other day and eight times a day.
Commonly wakes the person from sleep within 2 hours of going to sleep.
At least five episode of pain have occurred.
Headache is associated with at least one autonomic feature occurring on the same side as the pain.

Acute treatment for cluster headaches:
Subcutaneous or nasal triptan
High flow oxygen 12L/min - this should be set up at home

Prophylactic treatment:
Verapamil

Eg Question:
You are working in a neurology outpatient clinic seeing a patient referred from a local GP clinic. He’s a 42-year-old man who has been troubled by severe headaches over the past half a year. These headaches are the worse that he’s ever had in his life, describing them as far worse that the compound fracture he sustained three years ago. These headaches tend to happen most nights at around 2am just after he falls asleep. He often paces around his kitchen for a couple of hours and often resorts to bashing his head against the fridge the pain is so bad. When probed further he mentioned that he gets a sense of fullness in his right ear (which is the side that the headache most often occurs on). He remembers having a similar problem a couple of years ago that lasted a few months before resolving on their own.

What medication is most likely to prevent these headaches?

Question 49

Trigeminal Neuralgia - Differentials ! Example Question

Answer 49

A 64-year-old woman attends neurology clinic after referral from her GP with intermittent episodes of facial pain. She had first noticed symptoms around 10 months previously and recalled her first attack had occurred when taking her grand-children to a fireworks display. Pain episodes were described as a severe ‘sawing’ pain affecting the right side of her face that lasted one to two minutes before resolving completely. Since the onset the patient reported suffering from at least one attack on most days, with the frequency seeming to increase over time. On direct questioning she reported that on some occasions her nose had become blocked and she had felt sweaty during an episode but that these symptoms were not a major concern in comparison to the severe pain. The patient denied any other symptoms either at the time of the attack and was otherwise in good health with no recent history of weight loss. There was no family history of neurological disease.

A full neurological examination was performed with particular findings of normal pupillary reflexes, visual acuity and colour vision. There was no evidence of facial sensory deficit or facial nerve palsy. A peripheral neurological examination was likewise unremarkable.

Helpfully (although uncomfortably for the patient), a new episode of pain began during the course of the consultation. A further examination was conducted and conjunctival injection and slight eyelid oedema of the right eye were noted. In addition, the patient was noted to be sweating, markedly more profuse on the right side of her face. She also confirmed the onset of a blocked nose sensation at the onset of pain.

What is the most likely diagnosis causing the patients symptoms?

	Trigeminal neuralgia
	Multiple sclerosis
	Horners syndrome
	> Short unilateral neuralgiform pain with autonomic symptoms
	Atypical trigeminal neuralgia

The patients history certainly has features suggestive of trigeminal neuralgia, in particular the character and episodic nature of the pain and that the first episode was particularly memorable. However, the presence of autonomic features associated with attacks points strongly towards the variant short unilateral neuralgiform pain with autonomic symptoms (SUNA) as the correct diagnosis. The distinction is clinically relevant as individuals with autonomic symptoms achieved less benefit from microvascular decompression compared to individuals with trigeminal neuralgia.

Atypical trigeminal neuralgia is the diagnosis made when an individual suffers from persistent lower intensity pain between exacerbations, in contrast to the complete resolution of pain seen in trigeminal neuralgia. Horners syndrome would not cause episodic autonomic symptoms and is not normally associated with pain. Multiple sclerosis is an important differential for trigeminal neuralgia but the patients normal baseline neurological examination and prominent autonomic symptoms make this less likely. If uncertainty persists after clinical assessment, MRI scanning to assess for demyelination plaques is the appropriate investigation.

Question 50

Reversible Cerebrovascular Vasoconconstriction Syndrome (RCVS)

Answer 50

= Typical ‘thunderclap’ headache, with pain reaching a severe intensity within one minute of onset

Reversible cerebrovascular vasoconstriction syndrome (RCVS) is a cause of thunderclap headache with normal CT brain and normal or near-normal lumbar puncture results. RCVS may also be associated with focal neurological signs and seizures. Diagnosis is made by the finding of diffuse arterial beading on angiography (CT, MRI or catheter). One half of cases occur during the postpartum period or after exposure to serotoninergic agents, adrenergic substances or cannabis. There are no evidence based treatments for RCVS although bed-rest and nimodipine are usually prescribed. RCVS is not always benign, with one-in-four patients suffering sub-arachnoid haemorrhage or ischaemic / haemorrhagic stroke

Question 51

Thunderclap Headache Diagnosis - Example Question

Answer 51

A 32 year old man presented to the Emergency Department with a severe headache. The headache had started suddenly that evening while the patient was at home with his girlfriend watching television. The patient described his headache as an intense throbbing pain felt all across his head. The pain had started very quickly with the patient reporting a severity of 10 / 10 within 30 seconds. The pain had eased slightly following some morphine given by the ambulance crew. The patient denied any symptoms of neck stiffness or photophobia. There were no visual symptoms and no weakness in the patient’s limbs or abnormal sensation.

The patient had no previous past medical history and did not normally suffer from headaches. He took no regular medications. The patient worked as a retail assistant and lived with his girlfriend. He rarely drank alcohol but did smoke cannabis on several occasions each month. The patient’s girlfriend reported that the patient had smoked cannabis that evening prior to suffering his headache.

On examination, the patient was in visible discomfort due to his headache although had no meningitic signs. Glasgow Coma Score was 15/15 and the patient was afebrile. Cranial and peripheral nerve examination was unremarkable.

Further analgesia was given to the patient and investigations requested as detailed below.

CT brain: no evidence extra-dural or sub-dural bleeding; no intracerebral haemorrhage or sub-arachnoid blood; no evidence of cerebral infarction; normal ventricular system; no radiological contra-indication to lumbar puncture

Cerebrospinal fluid results:

Red cell count	1 / mm³
White cell count	2 / mm³
Pprotein	0.75 g / L
Glucose	60 % of serum value
Microscopy	No organisms seen
Red cell breakdown products	Negative
Opening pressure	19 cmCSF

Following initial investigation as above, the patient continued to experience severe recurrent headaches similar to that experienced at presentation and was observed to have a short, generalised seizure on the admission ward prompting further investigation.

CT angiography: diffuse arterial beading identified; results otherwise as for previous CT head

What is the cause for the patient’s headache?

Atypical migraine
Cervical artery dissection
> Reversible cerebrovascular vascoconstriction syndrome
Posterior reversible leucoencephalopathy syndrome
Pituitary apoplexy

The patient presents with a typical ‘thunderclap’ headache, with pain reaching a severe intensity within one minute of onset. Reversible cerebrovascular vasoconstriction syndrome (RCVS) is a cause of thunderclap headache with normal CT brain and normal or near-normal lumbar puncture results. RCVS may also be associated with focal neurological signs and seizures. Diagnosis is made by the finding of diffuse arterial beading on angiography (CT, MRI or catheter). One half of cases occur during the postpartum period or after exposure to serotoninergic agents, adrenergic substances or cannabis. There are no evidence based treatments for RCVS although bed-rest and nimodipine are usually prescribed. RCVS is not always benign, with one-in-four patients suffering sub-arachnoid haemorrhage or ischaemic / haemorrhagic stroke

The alternate answers listed in the stem are all causes of thunderclap headache with normal CT brain and lumbar puncture (i.e. sub-arachnoid haemorrhage excluded). None of these conditions area associated with diffuse arterial bleeding and so are less likely differential than RCVS.

Question 52

Migraine without Aura - Mx: Example Question

Answer 52

A 25-year-old female was seen in the neurology clinic with a six-year history of headaches. The headaches occur on average two to three times per week, and she described them as a one-sided pulsating headache with associated nausea and intolerance of light lasting for four-six hours before subsiding. The headaches worsened with exertion and when they occurred she would be disabled from continuing with normal daily activities, instead resorting to taking refuge in a darkened room. She denied the presence of any transient neurological deficit or facial lacrimation, and other than the associated photophobia she denied any ocular involvement. She denied the presence of weight loss or early morning headache. Her past medical history included hypothyroidism for which she was prescribed levothyroxine 125mcg OD.

Investigations conducted are as follows:

TSH 0.36 u/l

MRI: presence of normal intracranial appearances, no evidence of space occupying lesion, intracerebral haemorrhage or mass effect

She was trialled on propranolol 80mg M/R which reduced the frequency of the headaches, but unfortunately she did not tolerate the adverse effects. Which one of the following interventions is most appropriate to prevent the headaches from occurring?

	Amitryptyline
	Gabapentin
	Sodium valproate
	Increase dose of levothyroxine
	> Topiramate

This lady is suffering from migraines without aura. The NICE guidelines suggest that she is offered either propranolol or topiramate first line as migraine prophylaxis, and as she has not tolerated propranolol the next suitable option would, therefore, be topiramate. Note that topiramate like all antiepileptics is teratogenic and she would, therefore, need to be on suitable contraception prior to commencing topiramate. Gabapentin is suggested as a second line treatment option, and amitriptyline is only suggested as a prophylaxis option if the patient is already using amitriptyline and it is providing benefit. Her TSH is already suppressed sufficiently and so increasing the dose of levothyroxine would not be appropriate.

Question 53

Basilar Migraine

Answer 53

Basilar Migraine = a rare migraine subtype with aura

A large Danish study identified up to 10% of all non-hemiplegic migraineurs as basilar migraines, most of whom report a brainstem-associated range of symptoms lasting for around one hour1. 61% of patients report vertigo and over half dysarthria. One in four report episodes of loss of consciousness. Investigations include 24 hour tape and echocardiogram to exclude cardiac syncope and MRI to exclude posterior fossa space occupying lesion. An EEG may not exclude posterior epileptiform activity. Prevention can be offered with verapamil or topiramate.

Example Question:
A 32-year-old female presents with four episodes of loss of consciousness within the past 4 weeks. She denies palpitations or chest pain but reports sudden onset binocular black dots in visual fields, occasional flashing lights, dysarthria and hearing loss, all of which resolves after about 60 minutes. She is unsure about the relevance of an occipital headache, onset with frequency of about three times per week for the past year. She denies any limb weakness, altered sensation or facial droop. She has no past medical history or family history of epilepsy. Your neurological examination, including fundoscopy is unremarkable. An EEG is unremarkable. What is the likely diagnosis?

	Cluster headache
	Transient ischaemic attacks
	> Basilar migraine
	Bilateral retinal detachment
	Guillain-Barre syndrome

The symptoms are most likely to represent a rare migraine subtype with aura known as basilar migraine.

Question 54

Prevention of Post-Lumbar Puncture Headache - Example Question

Answer 54

A 25-year-old woman presented with a fronto-temporal headache, mild meningism and low-grade temperature. A CT head is normal and does not show any evidence of increased intra-cranial pressure. You consent the patient for an lumbar puncture, stating that a post-procedure headache is one of the most common procedures.
What is the most important preventative measure for a post-procedure headache?

> Re-insertion of the stylet prior to removing the needle
Ensure adequate hydration
Male patient gender
Patient position during the lumbar puncture
Bed-rest - lying supine post-procedure

A post-lumbar puncture headache occurs in 10 to 30% of patients following a lumbar puncture and is the most common complication. It is caused by the leakage of cerebrospinal fluid resulting in traction on the meninges.

Re-insertion of the stylet prior to removing the needle from the subarachnoid space can help prevent a post-lumbar puncture headache. Other factors such as male patient gender, small needle size and orientation of the needle bevel to be parallel to the longitudinal fibres of the dura have clearly been shown to decrease the incidence of post-lumbar puncture headache.

Hydration, position during and position post-procedure (bed rest), have not been shown to significantly decrease the risk of post-lumbar puncture headache.

Question 55

Migraine - Prevention in women of child-bearing age

Answer 55

Propranolol is preferable to topiramate in women of childbearing age (i.e. the majority of women with migraine)

Example Question:

A 27-year-old woman comes for review. She is having problems with increasingly frequent migraine attacks. These occur throughout her menstrual cycle and have no relation to her periods. She has tried a combination of paracetamol and ibuprofen to try and control the attacks but this seems to have had a limited effect. Her current medication includes paracetamol and ibuprofen as required and Cerazette (a progestogen-only pill).

What is the most appropriate medication to try and reduce the frequency of her migraine attacks?

> Propranolol
Zolmitriptan
Topiramate
Amitriptyline
Switch Cerazette to a combined oral contraceptive pill Propranolol is preferable to topiramate in women of childbearing age (i.e. the majority of women with migraine)

Zolmitriptan is useful to abort attacks but is not generally used for prophylaxis, except in the case of menstrual-related migraine (see below for more details). From the history it is clear that the headaches are not confined to the days around menstruation.

NICE recommend either propranolol or topiramate for migraine prophylaxis. Propranolol should be used in preference to topiramate in women of child bearing age as it may be teratogenic and it can reduce the effectiveness of hormonal contraceptives

The combined oral contraceptive pill is contraindicated given her history of migraine.

Question 56

Bilateral Transient Visual Loss - Example Question

Answer 56

A 36-year-old female presents to clinic with transient visual loss. She reports three episodes over the last few months where her ‘turns black’ in both eyes despite being alert. This lasts for a few seconds and is then followed by a unilateral throbbing headache associated with nausea and phonophobia. It is worse on exertion and lasts for a couple of days. On examination her visual acuity is 20/20 bilaterally, her visual fields are normal and fundoscopy is unremarkable.

What is the most likely diagnosis?

	Transient ischaemic attack
	Amaurosis fugax
	Anterior ischaemic optic neuropathy
	Temporal arteritis
	> Migraine with aura

The headache in this patient is very typical of migraine which can be receded by an aura lasting between 5 minutes to an hour usually. This patients visual loss was relatively brief and in the context of unilateral vision loss would certainly raise the possibility of transient ischaemic attack (TIA) However, she reports her vision turned black in both eyes which would be very unlikely with a TIA as there would have needed to be simultaneous involvement of both anterior visual pathways. Since there is isolated bilateral transient visual loss if this was a TIA it would be of the occipital cortex from occlusion of the posterior cerebral artery although this is very unlikely given it does not appear to be a homonymous hemianopia she describes, and there is a characteristic history of migraine which is the most common cause of transient bilateral visual loss in young adults. Amaurosis fugax specifies a type of TIA, which typically causes unilateral visual disturbance.

Temporal arteritis represents an arteritic form of anterior ischaemic optic neuropathy. Temporal arteritis tends to present later in life and may be associated with other symptoms like scalp tenderness, and jaw claudication. The non-arteritic form of anterior ischaemic optic neuropathy tends to be related to cardiovascular factors, and therefore again presents later in life and more commonly restricted to one eye.

Question 57

Cluster Headache Diagnosis and Mx - Example Question

Answer 57

You have been referred a 45-year-old man by the Accident and Emergency doctors with a severe headache. The headache woke him up at 3am, and he describes it as the worst headache he’s ever had. He has had two episodes like this over the past three days that have followed a very similar pattern, each lasting around 70 minutes before going. The pain is mainly around the left eye and temple and is sharp in nature. On examining him you note that his left eye is watering and swollen, and there’s some redness and mild bruising just above the eye. When you ask him about this bruising he says that the pain was so bad he bashed his head against the fridge door to try and help take it away.

How would you treat his headache?

	Oral triptan
	Indometacin
	100% oxygen and indometacin
	100% oxygen
	> 100% oxygen and nasal triptan

What is described above is the classical cluster headache. NICE guidelines characterise cluster headaches as one-sided headache in or around the eye or temporal region associated with signs of autonomic dysfunction on the same side.

Attacks of pain:
Usually last for 15-180 minutes
Almost always described as the most severe pain known
Tend to recur at the same time each day
Often wake the person shortly after falling asleep

Signs of symptoms of autonomic dysfunction include:
Rhinorrhoea or nasal congestion
Red eye and/or lacrimation
Facial or forehead sweating or flushing
Constriction of the pupil and/or ptosis
Eyelid oedema
A sense of aural fullness

The suggested first line treatment for cluster headaches is 100% oxygen at a flow rate of at least 12 litres per minute and a subcutaneous or nasal triptan. Evidence from one small study suggests that subcutaneous sumatriptan provides faster relief of symptoms than intranasal sumatriptan.

Indometacin is used in paroxysmal hemicrania which has similar characteristics to cluster headaches, but attacks tend to be shorter (2-45 minutes) and more frequent (up to 40/day) and more common in women.

Oral triptans have no evidence base in cluster headaches.

Question 58

Cluster Headache - Signs and Sx assoc with Autonomic Dysfunction

Answer 58

Signs of symptoms of autonomic dysfunction include:
Rhinorrhoea or nasal congestion
Red eye and/or lacrimation
Facial or forehead sweating or flushing
Constriction of the pupil and/or ptosis
Eyelid oedema
A sense of aural fullness

Question 59

Internal Carotid Artery Dissection

Answer 59

Internal carotid artery dissection can present with thunderclap headache, commonly following minor trauma.

Possible associated symptoms and signs include unilateral Horner’s syndrome, tinnitus or tongue palsy.

CT brain and lumbar puncture are usually normal with diagnosis confirmed by angiography.

Question 60

Vertebral Artery Dissection

Answer 60

Vertebral artery dissection can present with a thunderclap headache and would typically cause a posterior circulation stroke pattern of signs and symptoms.

Question 61

Reversible Cerebrovascular Vasoconstriction Syndrome

Answer 61

Reversible cerebrovascular vasoconstriction syndrome can present with a thunderclap headache and is associated with hypertension and seizures and diagnosed by arterial beeding on angiography.

Question 62

Posterior Reversible Encephalopathy Syndrome

Answer 62

Posterior reversible encephalopathy syndrome can present with thunderclap headache and is associated with hypertension and specific changes on MRI brain secondary to vasogenic brain oedema.

Posterior reversible leucoencephalopathy syndrome may present with thunderclap headache, usually followed rapidly by confusion, seizures and visual symptoms. CT brain and lumbar puncture results are usually normal or near normal. The most common causes of PRES are hypertensive encephalopathy and eclampsia. Hypertension is commonly observed.

Diagnosis is made by evidence of vasogenic brain oedema on MRI brain. PRES is often associated with reversible cerebrovascular vasoconstriction syndrome with vasospasms on angiography

Question 63

Posterior Communicating Artery Aneurysm

Answer 63

Posterior communicating artery aneurysm can present with a thunderclap headache and causes compression of the third nerve with unilateral mydriasis without other signs of third nerve palsy.

Question 64

Trigeminal Neuralgia - Pharmacological Therapy

Answer 64

Carbamazepine is the only drug licensed specifically for trigeminal neuralgia in the UK. In 70 % of patients it provides initial 100 % pain relief. However, caution must be used due to side-effects and drug interactions. Oxcarbazepine is a derivative of carbamazepine with similar efficacy but improved tolerability and side-effect profile.

In the evidence of allergy or intolerance to the above drugs then use of baclofen or lamotrigine should be considered, however the evidence base for both is thin. Gabapentin in combination with ropivacaine injections did show benefit in one randomised controlled trial but this result has not been replicated in subsequent investigations. Pregabalin had reported effectiveness in one prospective study of 53 patients

Question 65

Trigeminal Neuralgia - Surgical Indications

Answer 65

In around 95 % of cases, trigeminal neuralgia is believed to be caused by compression of the trigeminal nerve by adjacent blood vessels, although the exact mechanism of the pathophysiology is incompletely understood. In a minority of cases, trigeminal neuralgia can be due to an alternative diagnosis such as sinusitis, extra-cranial or intra-cranial masses, multiple sclerosis or infarction of the thalamus or brainstem which can all be diagnosed via MRI brain.

Using specialist techniques not included in the standard protocol, MRI can detect vascular contact with the trigeminal nerve. However, vascular contact with cranial nerves is also a normal variant in some individuals so these techniques are not routinely used.

In a patient who has long-standing and severe trigeminal neuralgia with life-limiting symptoms despite appropriate medical treatment surgical intervention should be considered and microvascular decompression is the surgical technique of choice and is effective treatment in 95 % of such cases of trigeminal neuralgia.

Question 66

Arnold Chiari Malformation Headache

Answer 66

Arnold Chiari malformation: occipital headache exacerbated by valsalva manoeuvre (coughing, sneezing and straining), pes cavus and cerebellar signs (past pointing and intention tremor in the upper limbs).