Comprehensive Review in Clinical Neurology: A Multiple Choice Question Book for the Wards and Boards

Chapter 4. Headache

Question

Questions 1–2

  1. An overweight 36-year-old woman presents with three to four severe, debilitating headaches per month for the last 2 years. The headaches last 1 to 2 days. They are sometimes localized bifrontally, but more often localized to the right temple, right frontal region, and behind the right eye. There is often rhinorrhea and congestion associated with her headaches. She denies any prodrome or auras. The pain is usually a deep ache, but throbbing when severe. She sometimes gets some nausea, but no vomiting. She has to wear sunglasses and go to a quiet room because she “can’t function.” What is the most likely diagnosis?

      a.  Cluster headache

      b.  Intermittent sinus headache

      c.  Episodic tension headache

      d.  Idiopathic intracranial hypertension (IIH; pseudotumor cerebri)

      e.  Episodic migraine

  2. Which of the following is not included in the International Classification of Headache Disorders—II (ICHD-II) criteria for episodic migraine?

      a.  Nausea/vomiting

      b.  Photophobia/phonophobia

      c.  Osmophobia

      d.  Worsening with activity

      e.  Pain severity/characterization

  3. A 41-year-old man presents with what you suspect to be tension-type headache. Which one of the following symptoms is included in the International Classification of Headache Disorders—II (ICHD-II) criteria for this disorder?

      a.  Photophobia

      b.  Throbbing/pulsating pain

      c.  Aggravation by routine physical activity

      d.  Nausea

      e.  Vomiting

  4. Which of the following would be the earliest step in the proposed pathophysiology of migraine?

      a.  Release of vasoactive neuropeptides from trigeminal sensory nerves

      b.  Meningeal blood vessel dilation

      c.  Activation of trigeminal sensory afferents in the meningeal vessels

      d.  Cortical spreading depression

      e.  Meningeal blood vessel constriction

Questions 5–6

  5. A 34-year-old overweight woman presents with a severe migraine that began 2 days ago, but is now nearly gone. She has not identified any triggers since these headaches began 2 years ago, has tried to avoid stress, and has kept a headache diary prior to her visit with you today. She averages about five migraines per month, each lasting 1 to 2 days. What is the best choice of treatment at this time, assuming there are no contraindications?

      a.  Prescribe sumatriptan and a NSAID to take immediately today to stop her resolving headache

      b.  Prescribe a preventative agent

      c.  Give her a dihydroergotamine (DHE) infusion today in the office

      d.  Follow her over the next couple of months before prescribing anything

      e.  Prescribe sumatriptan to use as needed, as well as a preventative agent

  6. The patient depicted in question 5 returns 1 week later. She is currently in a prolonged, severe headache phase that began 4 days ago and has missed 2 days of work. She recently got a new job at a law firm, and these headaches are beginning to interfere with her job. Her last triptan dose was 1 day ago. As you examine her head, you find that her right temporal and right frontal regions are exquisitely sensitive to touch. What is the best choice of treatment at this time, assuming there are no contraindications?

      a.  Increase her preventative medication dose and have her take another triptan

      b.  Change her preventative agent because it does not appear to be working

      c.  Give an IV dihydroergotamine (DHE) infusion

      d.  Change her triptan therapy and have her to take one now

      e.  Noncontrast brain CT to investigate the dysesthesia found on examination

  7. A 22-year-old mildly overweight woman presents to the emergency department with increasing frequency of previously diagnosed migraines. Other medical history is unremarkable with exception of mild asthma and recurrent constipation. The attacks are occurring 4 days per week and are lasting the entire day. What would be the best preventive medication to start in this patient?

      a.  Amitriptyline

      b.  Propranolol

      c.  Sumatriptan

      d.  Topiramate

      e.  Verapamil

  8. During an office visit, a 46-year-old man with a long-standing history of recurrent headaches is diagnosed for the first time with migraine. He has a history of anxiety, hypertension, hyperlipidemia, tobacco abuse, and is noncompliant with medications. Family history is significant for his mother having migraine and his father dying from a “heart attack” in his mid-fifties. If this patient presented to the emergency department at the very onset of a migraine, what would be the least optimal choice of treatment?

      a.  Sumatriptan

      b.  Ketorolac

      c.  Valproic acid

      d.  Prochlorperazine

      e.  IV magnesium

  9. A 39-year-old man presents to your office with the abrupt onset of severe holocephalic headache, nausea, and blurred vision about 4 hours ago. When asked, he admits that this is the worst headache he has ever had. He also reports some neck pain and says it feels stiff. He has a history of migraine, but says this headache is not like his normal migraine. What would be the next best course of action?

      a.  Dihydroergotamine (DHE) infusion to try to break this headache early

      b.  Intramuscular injection of ketorolac and consider prochlorperazine for nausea

      c.  Arrange for an urgent lumbar puncture (LP)

      d.  Obtain an urgent noncontrast brain CT

      e.  Subcutaneous injection of sumatriptan

10. The triptan medications are effective in treatment of migraine because they work at which of the following subreceptors?

      a.  Agonism at 5HT-2B, 5HT-2D

      b.  Antagonism at 5HT-1B, 5HT-1D

      c.  Agonism at 5HT-1B, 5HT-2D

      d.  Antagonism at 5HT-2B, 5HT-2D

      e.  Agonism at 5HT-1B, 5HT-1D

11. A 24-year-old woman with depression presents with a daily headache for the past 2 years. The headache began suddenly on November 14, 2008. She recalls it was on her birthday, but otherwise nothing out of the ordinary had happened. She reports being healthy, other than a mild sore throat the day before the onset of the headache, which is described as a daily, pressing, moderate, holocephalic pain. There is photophobia when the headache is exacerbated, but no visual or other neurologic symptoms. There is no postural component to the headache. She has had an MRI without and with contrast and an MRV, both normal. On the basis of the history, how would you classify this headache?

      a.  Tension-type headache

      b.  New daily persistent headache

      c.  Migraine without aura

      d.  Psychogenic headache disorder

      e.  Aseptic meningitis

12. The autonomic features of lacrimation, rhinorrhea, and nasal congestion seen in the trigeminal autonomic cephalalgias are due to the activation of which nucleus?

      a.  Parasympathetic outflow from the superior salivatory nucleus

      b.  Sympathetic outflow from the superior salivatory nucleus

      c.  Parasympathetic outflow from the nucleus solitarius

      d.  Parasympathetic outflow from the trigeminal nucleus caudalis (TNC)

      e.  Sympathetic outflow from the TNC

Questions 13–14

13. A 39-year-old woman presents with a 4-month history of headache. She reports it is only right sided, daily, and continuous since onset, with occasional lacrimation of the right eye. The pain is described as moderate, although exacerbations of severe pain occur. She also notes a sensation of grit in her right eye, and occasional paroxysmal and brief jabs and jolts on the right side of her head. She denies photophobia, phonophobia, nausea, vomiting, visual changes, or other neurologic features. How would you classify this headache?

      a.  Cluster headache

      b.  Paroxysmal hemicrania

      c.  Hemicrania continua

      d.  New daily persistent headache

      e.  Migraine without aura

14. What would be your first treatment of choice in this patient, assuming there are no contraindications?

      a.  Sumatriptan

      b.  Amitriptyline

      c.  Propranolol

      d.  Indomethacin

      e.  Topiramate

Questions 15–17

15. A 58-year-old man who does not typically get headaches presents to your office. He has a history of melanoma, which had been successfully treated. His headache has been worsening over the last month and has been constant. The pain is a deep ache around the left temporal and left frontal regions. He admits to mild intermittent low-grade fever and slight weight loss. He describes one episode in which he had some trouble seeing out of the left eye. He is worried because his mother had “some type of brain tumor.” Which of the following is not considered a “red flag” in evaluation of this headache?

      a.  Age

      b.  Family history of brain tumor

      c.  Fever

      d.  Weight loss

      e.  History of malignancy

16. On further questioning, he mentions that over the last 3 weeks he has been experiencing a cramp in his jaw while chewing and talking. On examination, you note that he is very sensitive to touch in the left temporal and scalp regions. What is the most likely diagnosis that should be first considered?

      a.  Tension-type headache

      b.  Brain tumor

      c.  Episodic migraine

      d.  Cluster headache

      e.  Temporal arteritis

17. What would be the next step in step in management?

      a.  β-blocker

      b.  Prednisone

      c.  Triptan

      d.  Temporal artery biopsy

      e.  Tricyclic antidepressant

18. A patient with a history of paroxysmal hemicrania (PH) has been reading about cluster headache on the internet and asks if that is what he has. You begin educating him on cluster headache. According to the International Classification of Headache Disorders—II (ICHD-II) criteria, the duration of a cluster headache is:

      a.  4 to 72 hours

      b.  1 to 60 minutes

      c.  1 to 60 seconds

      d.  15 to 180 minutes

      e.  1 to 12 hours

Questions 19–20

19. A 42-year-old woman presents with episodic headaches. Her headaches are described as severe attacks of unilateral periorbital pain lasting 10 minutes and associated with ipsilateral ptosis, lacrimation, conjunctival injection, and nasal congestion. She has more than five attacks daily for the majority of the time, and they usually occur during waking hours. There are no symptoms suggestive of an aura. What would be the best medication to try first?

      a.  High-flow oxygen during an attack

      b.  Sumatriptan

      c.  Verapamil

      d.  Indomethacin

      e.  Lithium

20. On the basis of the above history, how would you classify this headache?

      a.  Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT)

      b.  Migraine without aura

      c.  Paroxysmal hemicrania (PH)

      d.  Cluster headache

      e.  Hemicrania continua

21. Which of the following headache types is not currently considered a trigeminal autonomic cephalalgia by the International Classification of Headache Disorders—II (ICHD-II) criteria?

      a.  Paroxysmal hemicrania (PH)

      b.  Trigeminal neuralgia

      c.  Cluster headache

      d.  Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT)

      e.  Probable trigeminal autonomic cephalalgia

Questions 22–26

22. A 62-year-old man presents with episodes of left-sided facial pain. The episodes are brief and shock-like, lasting anywhere from several seconds up to a minute. They are located in the left cheek and are triggered by brushing his teeth and touching the area. What do you suspect on the basis of this history?

      a.  Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT)

      b.  Paroxysmal hemicrania (PH)

      c.  Cluster headache

      d.  Trigeminal neuralgia

      e.  Hemicrania continua

23. What would be the first-line treatment for this patient?

      a.  Lamotrigine

      b.  Carbamazepine

      c.  Lithium

      d.  Topiramate

      e.  Gabapentin

24. On the basis of your choice of treatment, which of the following adverse effects should be monitored for closely, especially when starting the medication?

      a.  Diabetes insipidus

      b.  Hypernatremia

      c.  Hyperkalemia

      d.  Hyponatremia

      e.  Metabolic acidosis

25. Which of the following medications could lead to an increased possibility of the adverse effect you are concerned about with your choice of treatment selected above?

      a.  Furosemide

      b.  Propranolol

      c.  Levetiracetam

      d.  Warfarin

      e.  Potassium supplementation

26. If this same presentation occurred in a 22-year-old woman with type I diabetes mellitus, what would be the most likely etiology that should be evaluated for?

      a.  Aneurysm

      b.  Arterial compression

      c.  Multiple sclerosis

      d.  Sarcoidosis

      e.  Neoplasm

27. A 42-year-old man complains of facial pain. He estimates about 100 attacks daily of severe, stabbing, periorbital pain, lasting about 20 seconds per attack. There is also prominent conjunctival injection and lacrimation associated with these attacks. What do you tell him you suspect as his diagnosis?

      a.  Cluster headache

      b.  Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT)

      c.  Trigeminal neuralgia

      d.  Paroxysmal hemicrania (PH)

      e.  Hemicrania continua

28. A 29-year-old woman with a history of depression presents with frequent headaches fitting the description of chronic tension-type. The location of her pain is occipital, slightly greater than frontal, and she has tenderness throughout the neck and shoulder musculature. There are no visual or neurologic symptoms or findings on examination. There are no exacerbating factors, such as postural changes or cough. She had an MRI of the brain 6 months ago, which reported a 4 mm Chiari I malformation. She is asking you if her symptoms are all from her Chiari I malformation and what should be done for it. What is the most appropriate next step in your evaluation and treatment plan?

      a.  Lumbar spine MRI to evaluate for spina bifida or other spinal malformations

      b.  Referral to neurosurgery to evaluate the possible role of suboccipital craniectomy and decompression

      c.  Repeat brain MRI to see if there has been progression of the Chiari malformation

      d.  Send her for physical therapy for the neck and shoulders and begin a preventative agent

      e.  Lumbar puncture (LP) for opening pressure and routine analysis

Questions 29–32

29. A 52-year-old man fell 5 ft from a ladder and landed on his back. His history is significant for recurrent pneumonia, and atrial fibrillation for which he takes warfarin. Later in the day, he began experiencing a bothersome headache located bifrontally. Other symptoms included stiff neck, nausea, photophobia, tinnitus, worsening on standing, and improvement on lying down. He has recently been healthy other than a worsening upper respiratory infection. Which of the following would be the most common diagnostic finding of your suspected diagnosis?

      a.  Lumbar puncture (LP) revealing significant leukocytosis

      b.  Brain CT showing cisternal blood

      c.  Brain MRI with gadolinium showing pachymeningeal enhancement

      d.  Neck CT angiogram showing an intramural hematoma in a carotid artery

      e.  Brain CT showing bifrontal crescentic hematomas

30. He is evaluated further with MRI of the brain. Using the MRI shown in Figures 4.1 and 4.2, what is the most likely diagnosis?

FIGURE 4.1 Coronal T1-weighted postcontrast MRI (Courtesy of Dr. Krishe Menezes)

FIGURE 4.2 Sagittal T1-weighted precontrast MRI (Courtesy of Dr. Krishe Menezes)

      a.  Early meningitis

      b.  SAH

      c.  Subdural hematoma

      d.  Carotid dissection

      e.  Low CSF pressure headache

31. Where is the most common location for the pathology leading to this type of headache?

      a.  Subdural space

      b.  Cervical spine

      c.  Thoracic spine

      d.  Distal ICA

      e.  Intracranial circulation, especially at an aneurysmal location

32. What is the most appropriate treatment of this patient?

      a.  Aneurysmal coiling if an endovascular approach is possible

      b.  Bed rest, hydration, caffeine, and epidural blood patch if conservative measures fail

      c.  Antibiotics and sending CSF for infectious etiologies

      d.  Neurosurgical evaluation and close monitoring for possible hematoma decompression

      e.  Anticoagulation

33. Which of the following treatments would be the least useful to use as an abortive agent in cluster headache?

      a.  Sumatriptan subcutaneous injection

      b.  Dihydroergotamine (DHE) subcutaneous injection

      c.  Zolmitriptan nasal spray

      d.  Frovatriptan tablets

      e.  Intranasal lidocaine

34. Which of the following treatments would be the least useful for cluster headache prevention during a cluster period?

      a.  Verapamil

      b.  Propranolol

      c.  Valproic acid

      d.  Lithium

      e.  Melatonin

Questions 35–40

35. A 26-year-old obese woman with borderline hypertension presents with worsening headache, which she describes as a bifrontal and bioccipital band-like pressure and pain. Occasionally, she experiences brief visual loss or graying, especially with straining, which lasts only seconds, but no photophobia or phonophobia. She sometimes gets nauseated and vomits when the pain is severe and she feels her vision is becoming increasingly blurred. What do you suspect may be the diagnosis?

      a.  Migraine

      b.  Tension-type headache

      c.  New daily persistent headache

      d.  Idiopathic intracranial hypertension (IIH)

      e.  Posterior fossa mass

36. Her fundoscopic examination of the left eye is shown in Figure 4.3. These findings are most consistent with which of the following?

FIGURE 4.3 Fundoscopy of left eye (Courtesy of Anne Pinter). Shown also in color plates

      a.  Acute optic neuritis

      b.  Normal examination

      c.  Posterior ischemic optic neuropathy

      d.  Papilledema

      e.  Anterior ischemic optic neuropathy

37. Topiramate is one treatment frequently used for this condition. What is the specific mechanism of action that makes topiramate useful as a treatment in this condition?

      a.  Sodium channel inhibition

      b.  NMDA antagonist

      c.  GABAA agonist

      d.  Kainate/AMPA antagonist

      e.  Carbonic anhydrase inhibitor

38. Which of the following is not a proposed mechanism in the pathogenesis of this condition?

      a.  Aqueduct stenosis

      b.  Decreased CSF absorption

      c.  Increased venous pressure

      d.  Increased CSF formation

      e.  Congenital stenosis of venous sinuses

39. Which of the following is not a treatment option for this condition?

      a.  Weight loss

      b.  Lumboperitoneal shunt

      c.  Ventriculoperitoneal shunt

      d.  Optic nerve fenestration

      e.  Hydrochlorothiazide

40. Which of the following would you not expect to find on physical examination in this condition?

      a.  Papilledema

      b.  Facial nerve palsy

      c.  Abducens nerve palsy

      d.  Visual loss (enlarging blind spot)

      e.  Elevated opening pressure

41. An overweight 41-year-old woman with hypertension, recurrent kidney stones, and increasing migraine frequency wishes to begin a preventive medication. Which of the following would be a poor choice to use?

      a.  Propranolol

      b.  Topiramate

      c.  Verapamil

      d.  Neurontin

      e.  Magnesium

Questions 42–45

42. A 47-year-old perimenopausal woman with a history of episodic migraine and prior idiopathic deep venous thrombosis in the right leg presents with a sudden-onset predominantly left-sided headache. She says it feels somewhat like her prior migraines, but the sudden onset and lack of photophobia and phonophobia are atypical for her. You notice on examination that venous pulsations are absent. What is this finding concerning for?

      a.  Diminished flow to the anterior circulation

      b.  Increased intracranial pressure

      c.  Diminished flow to the posterior circulation

      d.  Carotid cavernous fistula

      e.  Vasospasm

43. What is your suspected diagnosis on the basis of this information?

      a.  Episodic migraine with atypical features related to hormonal changes

      b.  SAH

      c.  Cerebral sinus venous thrombosis

      d.  Carotid dissection

      e.  Vertebral dissection

44. What test do you order next on the basis of your clinical suspicion?

      a.  Four-vessel angiogram

      b.  Brain and neck CT angiogram

      c.  Hypercoagulable profile

      d.  Brain MRV and MRI

      e.  Noncontrast brain CT

45. After your evaluation confirms the diagnosis, what is the standard therapy that should be started?

      a.  Aneurysmal coiling if endovascular approach is possible

      b.  Sumatriptan injection

      c.  Heparin

      d.  Decrease blood pressure with close monitoring of mean arterial pressure

      e.  Stenting the vessel

Questions 46–50

46. A 30-year-old man with a history of frequent migraine with aura has had several unclear TIAs. Family history reveals that his father also had migraine with aura and later developed an unknown neurologic disease. When questioned further, the patient says his father developed dementia in his fifties, had multiple strokes and TIAs, and lost the ability to walk, requiring a wheelchair shortly before his death at age 61. What diagnosis do you suspect?

      a.  Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS)

      b.  Recurrent migrainous cerebral infarction

      c.  Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

      d.  Primary CNS angiitis

      e.  Moyamoya disease

47. What chromosome is affected in this disorder?

      a.  21

      b.  3

      c.  17

      d.  19

      e.  11

48. What is the mode of genetic transmission for this disorder?

      a.  Autosomal recessive

      b.  X-linked dominant

      c.  Sporadic

      d.  Autosomal dominant

      e.  X-linked recessive

49. What would you expect to see on an MRI of the brain of a patient affected with this disorder?

      a.  Benign nonspecific white matter changes

      b.  Extensive intracranial stenosis with “puff of smoke” appearance

      c.  Extensive confluent deep white matter changes extending to the anterior temporal lobes

      d.  Alternating beading of intracranial vessels due to “skip” areas of stenosis

      e.  Ischemic areas throughout the basal ganglia

50. What gene is affected in this disorder?

      a.  NOTCH1 gene

      b.  Transfer RNA gene at mt3243

      c.  P/Q-type calcium channel receptor gene

      d.  NOTCH3 gene

      e.  CACNA1A gene

51. A 26-year-old woman has a history of migraine with aura that is often associated with hemiplegia lasting up to a day. Her mother has similar episodes with her migraine. Abnormalities in which of the following channels or channel subunits have not been associated with this disorder?

      a.  P/Q calcium channel subunit

      b.  Chloride channel subunit

      c.  A1A2 sodium–potassium ATPase channel

      d.  Presynaptic voltage-gated sodium channel

      e.  Postsynaptic voltage-gated sodium channel

52. A 43-year-old man comes to your clinic. He has had a 6-month persistent headache that is pounding and worse with bending down. He has had occasional episodes of confusion, but otherwise, is neurologically intact. An MRI of the brain shows diffuse leptomeningeal enhancement. CSF and blood testing have been negative for fungi, tuberculosis (TB), HIV, lupus, Lyme disease, and tumor cells. C- and P-ANCA (anti-neutrophil cytoplasmic antibodies) tests are negative. His CSF shows a mild lymphocytic pleocytosis. A leptomeningeal biopsy shows some perivascular inflammation, but no granulomas. You suspect that he has:

      a.  Wegener’s granulomatosis

      b.  Malignant angioendotheliomatosis

      c.  A remote effect of cancer

      d.  Idiopathic cranial pachymeningitis

      e.  Chemical meningitis

Answer Key

1. e

2. c

3. a

4. d

5. e

6. c

7. d

8. a

9. d

10. e

11. b

12. a

13. c

14. d

15. b

16. e

17. b

18. d

19. d

20. c

21. b

22. d

23. b

24. d

25. a

26. c

27. b

28. d

29. c

30. e

31. c

32. b

33. d

34. b

35. d

36. d

37. e

38. a

39. e

40. b

41. b

42. b

43. c

44. d

45. c

46. c

47. d

48. d

49. c

50. d

51. b

52. d

Answers

 1. e, 2. c

This patient fits the International Classification of Headache Disorders—II (ICHD-II) criteria for episodic migraine. She does not have aura, so this is episodic migraine without aura. Only 15% to 20% of patients with migraine have aura (classic migraine) as opposed to 80% to 85% who have migraine without aura (common migraine). Rhinorrhea and nasal congestion frequently coexist with migraine due to trigeminal cross-activation of the parasympathetics via stimulation of the superior salivatory nucleus of the facial nerve. Migraine is frequently misdiagnosed as sinus headache because of these “sinus-like” signs and symptoms. Primary headache disorders are not associated with an underlying pathologic process and include migraine, tension, cluster, and other trigeminal autonomic cephalalgias. Baseline neurologic examination is normal, and diagnostic workup is negative with primary headaches. Osmophobia is not included in the ICHD-II criteria for episodic migraine. The ICHD-II criteria for episodic migraine without aura include at least five headaches, each lasting 4 to 72 hours. The headache must have two of the four following criteria: unilateral location, pulsating quality, moderate-to-severe pain intensity, and worsening with physical activity. The headache must also be associated with one of the two following features: nausea and/or vomiting, or photophobia and phonophobia. Lastly, the symptoms cannot be attributable to another disorder.

 Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia. 2004; 24(Suppl. 1):9–160.

 3. a

The International Classification of Headache Disorders—II (ICHD-II) criteria for episodic tension-type headache include at least 10 attacks of headache lasting 30 minutes to 7 days. The headache must have two of the four following features: bilateral location, pressing/tightening (nonpulsating), mild-to-moderate pain intensity, and not worsened by routine physical activity. It must also have both of the following: no nausea/vomiting (anorexia may occur); no more than one of photophobia or phonophobia (either or neither, not both). Symptoms are not attributable to another disorder. Photophobia is the only option that is included in the criteria for tension-type headache in this patient. All others listed are criteria for migraine.

 Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia. 2004; 24(Suppl. 1):9–160.

 4. d

Of the choices listed, cortical spreading depression is felt to occur first. However, it is uncertain whether the trigger for cortical spreading depression occurs in the brain stem or within the cortex.

The pathophysiology of migraine is as follows:

1. Activation of hypersensitive “central generator” (it is debated whether the initiating trigger for migraine occurs in the cortex or in the brain stem) →

2. Disrupted ion homeostasis, release of neurochemicals, and transient dysfunction of neuronal function →

3. Meningeal blood vessel dilation and activation of trigeminovascular system →

4. Release of vasoactive neuropeptides (calcitonin gene-related peptide (CGRP), neurokinins, prostaglandins, substance P, etc.) from activated trigeminal sensory nerves leads to sterile neurogenic inflammation →

5. Worsening vasodilation, increasing firing of trigeminal afferents causing pain intensification →

6. Trigeminal nociceptive afferents carry pain signals to trigeminal nucleus caudalis (TNC) for processing and ascent through thalamus to cortex →

7. Continuous ascending pain signals activate more neurons leading to associated symptoms such as photo/phonophobia, nausea, and vomiting →

8. Continuous TNC firing, leads to central sensitization if activated pathways are not stopped

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

 5. e, 6. c

In the scenario depicted in question 5, this patient should have a triptan prescribed for abortive treatment at the earliest symptom identified for best effect. The abortive treatment should be combined with an NSAID for early treatment aimed at decreasing neurogenic sterile inflammation. If she still had a severe headache, dihydroergotamine (DHE) infusion would be an option, but unnecessary at this time because her headache is nearly resolved. It is crucial to treat migraine at the earliest symptoms identified. Optimal abortive treatment in the absence of vascular contraindications begins with a triptan. Concurrent administration of NSAIDs with the triptan decreases the neurogenic inflammation, the cause of worsening migraine symptoms. The purpose of the triptan is to reverse meningeal vasodilation, prevent release of vasogenic neuropeptides from the trigeminovascular system, and interfere with return of pain signals to the brain stem. The longer a patient waits to treat migraine, the less effective the acute treatments in reversing the entire complex of symptoms.

In addition, her headaches are severe, debilitating, occurring up to 10 days per month, and interfering with her job, so she should also be prescribed a preventative agent. Preventive therapy, if not previously started, should be initiated in migraine if the attacks are debilitating, severe (including presence of uncommon migraine findings, such as hemiplegic migraine, basilar migraine, and migrainous infarction), interfering with daily activities/jobs, and if there are greater than four migraines or ten headache-days per month. Preventive medication should be picked on the basis of comorbidities. In her case, she is overweight, so topiramate would be a reasonable choice because weight loss can be a side effect. Other examples would be a tricyclic antidepressant in depressed patients, β-blockers, or calcium-channel blockers in hypertensive patients.

In question 6, the patient now has had a migraine for more than 72 hours, so she is considered to be in status migrainosus and needs more aggressive therapy. The paresthesias represent cutaneous allodynia as a result of central sensitization related to the prolonged headache phase. IV DHE infusion would be reasonable and safe at this point because she has not had a triptan within the last 24 hours. Other IV medications commonly infused with DHE for additional benefit include antiemetics, magnesium, ketorolac, valproate sodium, and steroids. DHE, steroids, promethazine, and ketorolac can all be administered intramuscularly in the absence of infusion capability. Inhaled DHE is also available.

 Raskin NH. Modern pharmacotherapy of migraine. Neurol Clin. 1990; 8:857–865.

 Saper JR, Silberstein S. Pharmacology of dihydroergotamine and evidence for efficacy and safety in migraine. Headache. 2006; 46(Suppl. 4):S171–181.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

 7. d

Topiramate would be the best option and is the least contraindicated in this patient. The possible weight loss and appetite suppression side effect of topiramate would be beneficial for her. Other side effects to instruct the patient to be aware of when using topiramate include paresthesias in the digits, cognitive slowing, word-finding difficulty, kidney stone formation, and rarely, acute angle-closure glaucoma. The side effects of the remaining medications make them less desirable. Amitriptyline could cause weight gain in an already overweight patient. Propranolol and other β-blockers are contraindicated in patients with asthma, and can also cause weight gain and reduced exercise tolerance. Verapamil could worsen her constipation. Sumatriptan is used as an acute treatment of migraine, not as a preventive therapy.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

 8. a

Sumatriptan is contraindicated in patients with known coronary heart disease and should only be used after a cardiac workup if a patient has multiple cardiac risk factors. This patient has several cardiovascular risk factors, such as uncontrolled hypertension, hyperlipidemia, tobacco abuse, gender, age, and a family history of early heart disease. This patient would require a full cardiac evaluation (including a stress test), prior to any use of triptans, and they would still be used only cautiously with the first dose administered in the office if his risk factors were controlled and cardiac evaluation showed no evidence of cardiac ischemia. Combinations of various antiemetics, anti-inflammatories, anticonvulsants, and magnesium are all commonly used as acute treatments of migraine, especially when the preferred treatment with triptans is not an option. A new class of migraine medication called calcitonin gene-related peptide (CGRP) inhibitors is proposed to be safe for the acute treatment of migraine in those with cardiac risk factors, in which triptans would otherwise be contraindicated.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

 Tepper SJ. Safety and rational use of the triptans. Med Clin North Am. 2001; 85:959–970.

 9. d

This man gives the history of an abrupt-onset thunderclap headache. Patients usually admit that it is the “worst headache of their life.” The current headache does not reflect his normal migraine pattern or quality and warrants further investigation. A noncontrast brain CT scan is necessary to evaluate for SAH. If brain CT scan is negative but suspicion remains high, a lumbar puncture (LP) should be performed. CT sensitivity for detecting SAH is highest in the first 12 hours after SAH (nearly 100%), is about 92% sensitive for SAH within 24 hours, and it falls to around 58% by the end of day 5 postbleed. LP is best performed at least 6 hours after symptom onset and becomes very low yield at 3 weeks. If LP is obtained, an opening pressure should be measured, and the CSF should be sent for cell counts in tubes 1 and 4, protein, glucose, xanthochromia, and gram stain.

 Latchaw RE, Silva P, Falcone SF. The role of CT following aneurysmal rupture. Neuroimaging Clin N Am. 1997; 7:693–708.

 Sames TA, Storrow AB, Finkelstein JA, et al. Sensitivity of new-generation computed tomography in subarachnoid hemorrhage. Acad Emerg Med. 1996; 3:16–20.

 Sidman R, Connolly E, Lemke T. Subarachnoid hemorrhage diagnosis: lumbar puncture is still needed when the computed tomography scan is normal. Acad Emerg Med. 1996; 3:827–831.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

10. e

The triptans work as agonists at the serotonin receptor subtypes 5HT-1B and 5HT-1D. Agonism at 5-HT1B receptors constricts the pain-producing intracranial, extracerebral blood vessels in the meninges. Agonism at 5-HT1Dreceptors presynaptically inhibits trigeminal peptide release and interferes with central trigeminal nucleus caudalis (TNC) nociceptive transduction and processing, whereas those of the nucleus tractus solitarius in the brain stem are thought to inhibit nausea/vomiting. Ultimately, these effects result in reversal of vasodilation, decrease in neurogenic inflammation, reduction of central nociceptive signal transmission to the thalamus and cortex, and cessation of other ascending pathways to the cortex, which result in associated migrainous symptoms, such as photophobia and phonophobia.

 Tepper SJ. Safety and rational use of the triptans. Med Clin North Am. 2001; 85:959–970.

 Tepper SJ, Millson D. Safety profile of the triptans. Expert Opin Drug Saf. 2003; 2:123–132.

11. b

This headache fits the criteria for new daily persistent headache (NDPH). This primary headache typically begins abruptly, and patients often recall the exact date it started. Examination and evaluations are normal. It does not fit criteria for the other headache types listed. A psychogenic etiology is a diagnosis of exclusion, and aseptic meningitis would not be this prolonged. Other considerations for abrupt onset of daily headache include a CSF leak, excluded by a lack of pain with postural changes and absence of pachymeningeal enhancement on MRI; and venous sinus thrombosis, excluded by the normal MRV.

The International Classification of Headache Disorders—II (ICHD-II) criteria for NDPH include a headache that, within 3 days of onset, is present daily, and is unremitting, for more than 3 months. It must have at least two of the four following criteria: bilateral location, pressing/tightening (nonpulsating) quality, mild-to-moderate pain intensity, and not worsened by routine physical activity, such as walking or climbing. In addition, it must also have both of the following: no more than one of photophobia, phonophobia, or mild nausea; neither moderate or severe nausea nor vomiting. Lastly, symptoms are not attributable to another disorder.

 Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia. 2004; 24(Suppl. 1):9–160.

12. a

Parasympathetic outflow from the superior salivatory nucleus of cranial nerve VII leads to activation of lacrimal and nasal mucosal glands. Parasympathetic fibers travel with the greater superficial petrosal nerve of cranial nerve VII to the sphenopalatine ganglion, synapse, and then travel with the maxillary division of cranial nerve V to the lacrimal glands. Parasympathetic fibers also travel in the lesser superficial petrosal nerve of cranial nerve VII to the otic ganglia. There is a brainstem connection between the trigeminal nucleus caudalis and the superior salivatory nucleus causing the trigeminal-autonomic reflex. This reflex is activated by a noxious stimulus applied to the trigeminal distribution. For example, getting hit in the face with a ball will cause lacrimation and rhinorrhea.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

 Tubbs RS, Menendez J, Loukas M, et al. The petrosal nerves: anatomy, pathology, and surgical considerations. Clin Anat. 2009; 22:537–544.

13. c, 14. d

This patient’s history is consistent with hemicrania continua. This primary headache is more common in women and is one of several “indomethacin-responsive” headaches, with others being paroxysmal hemicrania (PH), primary cough headaches, primary stabbing headaches, and for some patients, primary headaches associated with sexual activity. Therefore, indomethacin should be the first medication tried. In order to rule out incomplete response, indomethacin should be used in a dose of ≥150 mg daily orally for at least a week, but for maintenance, smaller doses are often sufficient. It is reasonable to obtain an MRI and MRA of the brain with and without gadolinium with thin cuts through the cerebellopontine angle and Meckel’s cave in patients presenting with suspected involvement of the trigeminal nerve, as in hemicrania continua, trigeminal neuralgia, or any of the trigeminal autonomic cephalalgias.

The International Classification of Headache Disorders—II (ICHD-II) criteria for hemicrania continua consist of a headache for more than 3 months. It must have all of the following criteria: unilateral pain without side shift, daily and continuous without pain-free periods, and moderate intensity, but with exacerbations of severe pain. It must have at least one of the following autonomic features during exacerbations and ipsilateral to the side of pain: conjunctival injection and/or lacrimation, nasal congestion and/or rhinorrhea, and ptosis and/or miosis. A complete response to therapeutic doses of indomethacin should be seen, and the headache is not attributable to another disorder.

Cluster headache and paroxysmal hemicrania (PH) are discussed in further questions. Migraine was discussed in questions 1 and 2, and new daily persistent headache (NDPH) in question 11.

 Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia. 2004; 24(Suppl. 1):9–160.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

15. b, 16. e, 17. b

Headache red flags include systemic symptoms (fever, chills, and weight loss), history of prior cancer or immunodeficiency, focal neurologic signs or symptoms, new headache with onset to peak of seconds to minutes (thunderclap), “first or worst headache,” new-onset headache after age 50, precipitation by exertion, strain, or positional changes, increasing headache frequency and severity, and new-onset seizures. Secondary headache disorders have many possible etiologies and are related to an underlying pathologic process. They are associated with an abnormal neurologic examination and/or abnormal diagnostic workup. A family history of brain tumor is not considered a typical “red flag.” A common mnemonic used for headache red flags is SNOOP:

Systemic symptoms (fever, chills, and weight loss) or secondary headache risk factors (HIV and cancer)
Neurologic symptoms or signs (confusion, impaired consciousness, and focal findings)
Older: new-onset or progressive headache, especially >50 years old (temporal arteritis)
Onset: sudden, abrupt (thunderclap)
Progression of headache (change in frequency, severity, or clinical features)

Temporal arteritis (giant-cell arteritis) often presents in persons older than 50 years of age. It is associated with jaw claudication and headache usually localized to the temple region, although it may be nonlocalized. Constitutional symptoms are often present, such as fever and weight loss. The patient may also complain of visual disturbances, including visual loss. Patients with suspected temporal arteritis should have an ESR checked. ESR is usually greater than 50 to 60 mm/h in temporal arteritis. Diagnosis is confirmed by temporal artery biopsy. On suspicion of this diagnosis, prednisone 60 to 80 mg daily should be started to prevent permanent visual loss, even before biopsy confirmation. It is also worth noting that this patient has a previous history of melanoma, which can recur and commonly metastasize to the brain. For that reason, MRI with and without contrast should be obtained (melanoma metastases are notoriously vascular). See discussion to question 18 for cluster headache, question 3 for tension-type headache, and questions 1 and 2 for migraine.

 Dodick DW. Clinical clues and clinical rules: primary vs secondary headache. Adv Stud Med. 2003; 3(6 C):S550–S555.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

 Silberstein SD, Stiles MA, Young WB. Atlas of Migraine and Other Headaches, 2nd ed. London and New York: Taylor and Francis Group; 2005.

18. d

The duration of a cluster headache is 15 to 180 minutes. The International Classification of Headache Disorders—II (ICHD-II) criteria for cluster headache require at least five attacks fulfilling the following: severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes if untreated. The headache must be associated with at least one of the following: ipsilateral conjunctival injection and/or lacrimation, ipsilateral nasal congestion and/or rhinorrhea, ipsilateral eyelid edema, ipsilateral forehead and facial sweating, ipsilateral miosis and/or ptosis, a sense of restlessness, or agitation. Attacks occur at a frequency of 1 every other day to 8 per day, and symptoms are not attributable to another disorder.

 Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia. 2004; 24(Suppl. 1):9–160.

19. d, 20. c

This is paroxysmal hemicrania (PH), one of the “indomethacin-responsive” headaches (see question 13). Therefore, indomethacin should be the first medication tried. In order to rule out incomplete response, indomethacin should be used in a dose of ≥150 mg daily orally for at least a week, but for maintenance, smaller doses are often sufficient. As with hemicrania continua, PH is more common in women. Of note, PH often gets confused with cluster headache. Differentiating features of PH include shorter-lasting and more frequent attacks, as well as a complete response to indomethacin.

The International Classification of Headache Disorders—II (ICHD-II) criteria for PH require at least 20 attacks of severe unilateral orbital, supraorbital, or temporal pain lasting 2 to 30 minutes. The headache is accompanied by at least one of the following: ipsilateral conjunctival injection and/or lacrimation, ipsilateral nasal congestion and/or rhinorrhea, ipsilateral eyelid edema, ipsilateral forehead and facial sweating, ipsilateral miosis and/or ptosis. The attacks have a frequency of more than 5 per day for more than half of the time, although periods with lower frequency may occur. The attacks are prevented completely by therapeutic doses of indomethacin, and the headache is not attributable to another disorder. See discussion to question 27 for short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT), question 1 for migraine, question 18 for cluster headache, and question 13 for hemicrania continua.

 Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia. 2004; 24(Suppl. 1):9–160.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

21. b

Trigeminal neuralgia is not associated with autonomic features and is therefore not classified as a trigeminal autonomic cephalalgia. It is currently classified in the International Classification of Headache Disorders—II (ICHD-II) criteria as one of the “cranial neuralgias, facial pain and other headaches.” The headaches that are classified as one of the “cluster headache and other trigeminal autonomic cephalalgias” include cluster headache, paroxysmal hemicrania (PH), short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT), and probable trigeminal autonomic cephalalgia.

 Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia. 2004; 24(Suppl. 1):9–160.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

22. d, 23. b, 24. d, 25. a, 26. c

This is a classic presentation of trigeminal neuralgia. The first-line treatment is carbamazepine, although the other choices have been reported as beneficial (except for lithium) if carbamazepine is contraindicated or ineffective. Hyponatremia is the most common side effect seen with carbamazepine. If the patient is taking diuretics such as furosemide, the risk of hyponatremia will increase. Serum sodium levels should be monitored for the first few months of treatment. If a young woman presented with the same symptoms, multiple sclerosis should be evaluated for, especially with bilateral trigeminal neuralgia.

The International Classification of Headache Disorders—II (ICHD-II) criteria for trigeminal neuralgia include paroxysmal attacks of pain lasting from a fraction of a second to 2 minutes, affecting one or more divisions of the trigeminal nerve. The pain has at least one of the following characteristics: intense, sharp, superficial, or stabbing, and precipitated from trigger areas or by trigger factors. Attacks are stereotyped, there is no clinically evident neurologic deficit, and symptoms are not attributable to another disorder. See discussion to question 27 for short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT), question 18 for cluster headache, question 13 for hemicrania continua, and question 19 for paroxysmal hemicrania (PH).

 Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia. 2004; 24(Suppl. 1):9–160.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

27. b

This patient is describing episodes of short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). This is a very rare primary headache disorder, more common in males, and can easily be confused with trigeminal neuralgia and other trigeminal autonomic cephalalgias. Trigeminal neuralgia does not have associated autonomic features and is discussed in question 22. Following a painful paroxysm in trigeminal neuralgia, there is usually a refractory period during which pain cannot be triggered, whereas this refractory period is not seen in SUNCT. SUNCT is rare enough that an MRI without and with contrast to rule out secondary causes, especially pituitary tumors, is mandatory.

The International Classification of Headache Disorders—II (ICHD-II) criteria for SUNCT must include at least 20 attacks characterized by the following: attacks of unilateral orbital, supraorbital, or temporal stabbing or pulsating pain lasting 5 to 240 seconds, the pain is accompanied by ipsilateral conjunctival injection and lacrimation, attacks occur with a frequency from 3 to 200 per day, and symptoms are not attributable to another disorder.

 Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia. 2004; 24(Suppl. 1):9–160.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

28. d

It is very unlikely that this patient’s headaches are related to her Chiari I malformation. Chiari I is defined as tonsillar herniation below the level of foramen magnum, and it may be associated with syringomyelia (50%-70%) and hydrocephalus. When headaches are related to Chiari malformation, it is due to compression of neural tissues and alteration of CSF dynamics. The headaches are usually in the occipital region and precipitated paroxysmally by cough, bending forward, and valsalva maneuvers. When symptomatic, there are other symptoms of brainstem compression or cervical cord compression, such as ataxia, visual disturbances, hoarseness, dysphagia, vertigo, nystagmus, hearing loss, and cervical myelopathy. The upper limits of normal for tonsillar descent by age are as follows: 6 mm for ages 0 to 10 years, 5 mm for ages 10 to 30 years, 4 mm for ages 30 to 80 years, and 3 mm for ages older than 80 years. This patient has no neurologic features or symptoms consistent with a symptomatic Chiari, and her imaging is within the acceptable range. Her neck and shoulder musculature tenderness may be contributing to her tension-type headache, and physical therapy should be arranged. In addition, contributors such as stress, depression, and caffeine overuse should be assessed and addressed. She might benefit from preventive therapy at this time, and an antidepressant, such as amitriptyline, would be a good consideration.

 Mikulis DJ, Diaz O, Egglin TK, et al. Variance of the position of the cerebellar tonsils with age: preliminary report. Radiology. 1992; 183:725–728.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

29. c, 30. e, 31. c, 32. b

Although all of the mentioned options are included in the differential diagnosis, the history of trauma and positional quality to the headache suggest traumatic CSF leak and subsequent low-CSF-pressure headache, which is what this patient has. Some causes of low-CSF-pressure headache include lumbar puncture (LP), neurosurgical procedures, dural tear from spondylosis, and meningeal diverticuli. The most common location of spontaneous CSF leaks is at the level of the thoracic spine. An MRI of the brain with gadolinium will often show pachymeningeal enhancement (as seen in Figure 4.1) and downward displacement of the brain and crowding of the posterior fossa due to the sagging and traction of intracranial structures and dura, which may mimic Chiari I malformation (as seen in Figure 4.2). Neuroimaging may also reveal subdural hematomas or hygromas, engorgement of cerebral venous sinuses, pituitary enlargement, flattening of the optic chiasm, increased anteroposterior diameter of the brainstem, and decrease in the size of cisterns and ventricles. Other evaluations helpful in the diagnosis include low opening pressure on spinal tap, radioisotope cisternography, and CT myelography. Conservative measures include bed rest, hydration, and caffeine. If these measures fail, an epidural blood patch should be performed. Surgical repair of the dural defect is done as a last resort.

The International Classification of Headache Disorders—II (ICHD-II) criteria for headache attributed to spontaneous low CSF pressure consist of a diffuse and/or dull headache that worsens within 15 minutes after sitting or standing. The headache must also have at least one of the following criteria: neck stiffness, tinnitus, hypacusia, photophobia, or nausea. It must also have at least one of the following: evidence of low CSF pressure on MRI (e.g., pachymeningeal enhancement), evidence of CSF leakage on conventional myelography, CT myelography or cisternography, or CSF opening pressure <60 mm H2O in sitting position. There should be no history of dural puncture or other cause of CSF fistula, and the headache resolves within 72 hours after epidural blood patching.

 Chung SJ, Lee JH, Kim SJ, et al. Subdural hematoma in spontaneous CSF hypovolemia. Neurology. 2006; 67:1088–1089.

 Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia. 2004; 24(Suppl. 1):9–160.

 Marcelis J, Silberstein SD. Spontaneous low cerebrospinal fluid pressure headache. Headache. 1990; 30:192–196.

 Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA. 2006; 295:2286–2296.

 Spelle L, Boulin A, Tainturier C, et al. Neuroimaging features of spontaneous intracranial hypotension. Neuroradiology. 2001; 43:622–627.

33. d

Frovatriptan would be a poor choice for acute treatment of cluster headache, although it has been used for preventive purposes during cluster periods. Frovatriptan has a half-life of around 26 hours and a slower onset of action than sumatriptan, zolmitriptan, rizatriptan, almotriptan, and eletriptan. Any medication taken by mouth is a poor choice for acute treatment of cluster headache because cluster attacks peak very rapidly, so a fast onset of action is needed to abort the headache quickly. Triptans can be used, but the choice would need to be a formulation with a rapid onset of action, such as sumatriptan subcutaneous injections, sumatriptan nasal spray, or zolmitriptan nasal spray. Sumatriptan subcutaneous needle-free drug delivery system may also be used. Oxygen is very effective as an abortive for cluster and is often used as a first-line treatment. All of the other choices listed above, except for frovatriptan, are used for acute treatment of cluster.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

 Silberstein SD, Stiles MA, Young WB. Atlas of Migraine and Other Headaches, 2nd ed. London and New York: Taylor and Francis Group; 2005.

34. b

Cluster headache preventive therapy should be started immediately at the beginning of a cluster period in episodic cluster. If the cluster periods become chronic (<1 month headache-free period per year) or are significantly increasing in duration, preventive therapy should be continued indefinitely. Preventive therapy should be thought of as “verapamil plus.” In other words, verapamil should be first line and other agents added to it. All of the choices except for propranolol are used as cluster preventives. Melatonin levels have been shown to be decreased during cluster periods, so melatonin can also be used in high doses (up to 15 mg) during cluster periods, although positive randomized-controlled studies are lacking.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

 Silberstein SD, Stiles MA, Young WB. Atlas of Migraine and Other Headaches, 2nd ed. London and New York: Taylor and Francis Group; 2005.

35. d, 36. d, 37. e, 38. a, 39. e, 40. b

This patient’s history suggests idiopathic intracranial hypertension (IIH) or pseudotumor cerebri. It occurs most commonly in young, overweight women. Topiramate is used because of its carbonic anhydrase inhibitor effect; it decreases CSF production. Acetazolamide is the classic carbonic anhydrase inhibitor used, unless the patient has a sulfa allergy, which would make topiramate a better choice. Of the possible etiologies listed, aqueductal stenosis is not a cause of idiopathic intracranial hypertension (IIH), although it would be a secondary cause of hydrocephalus. Treatment typically begins conservatively with measures such as weight loss, cessation of vitamin A (if toxicity is suspected), weaning steroids, and minimizing other potential risks. If there is no evidence of visual loss, some feel that treatment of the headache alone is sufficient. If there is evidence of visual loss, a carbonic anhydrase inhibitor such as acetazolamide or topiramate should be started. Hydrochlorothiazide is not a typical treatment for IIH.

The fundoscopic examination is consistent with papilledema. An early finding of increased intracranial pressure preceding papilledema is loss of spontaneous venous pulsations, although this can also be a normal variant. Disc margin splinter hemorrhages may be seen early also. Eventually, the disc becomes elevated, the cup is lost, and the disc margins become indistinct. Blood vessels appear blurred as they course the disc. Engorgement of retinal veins lead to a hyperemic disc. As the edema progresses, the optic nerve head appears enlarged and may be associated with flame hemorrhages and cotton wool spots, as a result of nerve fiber infarction. The photograph does not show optic neuritis (see Chapter 1), anterior ischemic optic neuropathy (AION) (see Chapter 1), or posterior ischemic optic neuropathy (see Chapter 1).

Procedures should generally be performed when there is progressive visual field defect, visual acuity loss from papilledema, and intractable headache while on maximal pharmacotherapy. Optic nerve fenestration can be done if visual loss is progressive on pharmacotherapy. Serial high-volume lumbar puncture (LP) has fallen out of favor because of the short-lasting effect and unnecessary patient discomfort and inconvenience. There are no studies suggesting clinical benefit from weight loss, although this is commonly recommended. Procedures performed as a last resort include lumboperitoneal or ventriculoperitoneal shunt. Most patients with idiopathic intracranial hypertension (IIH) have a headache, but not all. They may complain of transient visual obscurations (seconds), graying of vision (especially with straining), diplopia (cranial nerve VI palsy), bilateral pulsatile tinnitus, nausea, and vomiting. Examination findings may include those listed in question 40, especially papilledema, visual field loss, or decreased venous pulsations. Facial nerve palsy would not be an associated finding.

The International Classification of Headache Disorders—II (ICHD-II) criteria for IIH include a progressive headache with at least one of the following characteristics: daily occurrence, diffuse and/or constant (nonpulsating) pain, aggravated by coughing or straining. Intracranial hypertension in an alert patient should demonstrate a neurologic examination that either is normal or shows any of the following abnormalities: papilledema, enlarged blind spot, visual field defect (progressive if untreated), or abducens nerve palsy. There should be increased CSF pressure (>200 mm H2O in the nonobese, >250 mm H2O in the obese) measured by LP in the recumbent position or by epidural or intraventricular pressure monitoring. There should be normal CSF chemistry (low CSF protein is acceptable) and cellularity. Intracranial diseases (including venous sinus thrombosis) are ruled out by appropriate investigations, and no metabolic, toxic, or hormonal cause of intracranial hypertension should be present. The headache develops in close temporal relation to increased intracranial pressure, and the headache improves after withdrawal of CSF to reduce pressure to 120 to 170 mm H2O and resolves within 72 hours of persistent normalization of intracranial pressure.

 Acheson JF, Green WT, Sanders MD. Optic nerve sheath decompression for the treatment of visual failure in chronic raised intracranial pressure. J Neurol Neurosurg Psychiatry. 1994; 57:1426–1429.

 Burgett RA, Purvin VA, Kawasaki A. Lumboperitoneal shunting for pseudotumor cerebri. Neurology. 1997; 49:734–739.

 Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia. 2004; 24(Suppl. 1):9–160.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

41. b

Topiramate is often used in overweight patients because it can be associated with weight loss, but given that this patient has a history of recurrent kidney stones, topiramate becomes a poor choice. All of the other choices have been shown to be beneficial for preventive purposes and are commonly used. Because she is hypertensive, a β-blocker or calcium-channel blocker would be a good treatment option. Preventive therapy should always be targeted not only for headache prevention, but also for any comorbidities that are present.

 Peikert A, Wilimzig C, Kohne-Volland R. Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia. 1996; 16:257–263.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

42. b, 43. c, 44. d, 45. c

This patient’s history is concerning for a cerebral venous sinus thrombosis, especially in the setting of prior idiopathic deep venous thrombosis (DVT), which may suggest an underlying hypercoagulable state. Absent venous pulsations suggests elevated intracranial pressure, which can be the result of cerebral venous sinus thrombosis. Besides headache, other symptoms may include seizures, encephalopathy, focal neurologic findings, papilledema, and vomiting. Although a hypercoagulable panel should be checked, the more immediate testing should be a brain MRV and MRI to look for venous sinus filling defects. If imaging confirms the diagnosis, heparin should be started with transition to warfarin. It is important to obtain the hypercoagulable workup prior to starting warfarin, because this medication may alter the results of these blood tests. Other risk factors include oral contraceptive use (especially in conjunction with smoking), pregnancy, infection, head trauma, and malignancy. Treatment duration varies between 3 and 6 months, but if the hypercoagulable workup is positive, lifelong anticoagulation may be needed.

 Bousser MG, Russell RR. Cerebral venous thrombosis. In: Major Problems in Neurology, Warlow CP, Van Gijn, J (Eds), London, UK: WB Saunders; 1997.

 Ferro JM, Canhão P, Stam J, et al; ISCVT Investigators. Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke. 2004; 35:664–670.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

46. c, 47. d, 48. d, 49. c, 50. d

This patient’s history and family history are suggestive of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This disorder presents with migraine with aura, stroke or stroke-like episodes, progressive dementia, and other neurodegenerative findings. This is an autosomal dominant disorder most often due to a missense mutation in the NOTCH3 gene, on chromosome 19q13.1, although splice site mutations and small in-frame deletions have also been reported. The NOTCH3 gene encodes a transmembrane protein thought to be involved in cell signaling during embryonic development. It can be diagnosed by genetic testing or skin biopsy. MRI of the brain will show confluent deep white matter changes. These deep white matter changes may characteristically affect the anterior temporal lobes.

 Dichgans M, Mayer M, Uttner I, et al. The phenotypic spectrum of CADASIL: clinical findings in 102 cases. Ann Neurol. 1998; 44:731–739.

 Joutel A, Vahedi K, Corpechot C, et al. Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. Lancet. 1997; 350:1511–1515.

 Peters N, Opherk C, Bergmann T, et al. Spectrum of mutations in biopsy-proven CADASIL: implications for diagnostic strategies. Arch Neurol. 2005; 62:1091–1094.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

51. b

This patient’s presentation and history suggest hemiplegic migraine. Although there are sporadic forms, she likely falls into the category of familial hemiplegic migraine (FHM) given her mother’s history. There are three types of FHM that are all autosomal dominant with variable penetrance. FHM1 is linked to chromosome 19p13 (CACNA1A gene), resulting in a defect in P/Q calcium-channel subunit. Additional FHM1 symptoms may include cerebellar involvement, such as gaze-evoked nystagmus or ataxia, also attacks of coma, prolonged hemiplegia, or both, but full recovery is the rule. Transient cerebral edema and cerebral atrophy are less commonly seen. FHM2 is linked to 1q23 (ATP1A2 gene), resulting in a defect in the A1A2 sodium–potassium ATPase channel. Additional FHM2 symptoms may include recurrent coma, frequent and long-lasting hemiplegia, or seizures with mental retardation. Cerebellar ataxia is not associated with FHM2. FHM3 is linked to chromosome 2q24 (SCN1A gene), resulting in defects of presynaptic and postsynaptic voltage-gated sodium channels.

 Dichgans M, Freilinger T, Eckstein G, et al. Mutation in the neuronal voltage-gated sodium channel SCN1 A in familial hemiplegic migraine. Lancet. 2005; 366:371–377.

 Jen JC, Kim GW, Dudding KA, et al. No mutations in CACNA1 A and ATP1A2 in probands with common types of migraine. Arch Neurol. 2004; 61:926–928.

 Silberstein SD, Lipton RB, Dodick D, et al. Wolff’s Headache and Other Head Pain, 8th ed. New York: Oxford University Press; 2008.

52. d

This patient has an idiopathic cranial pachymeningitis. In this syndrome, patients experience headache as well as other neurologic symptoms such as hemiparesis, ataxia, aphasia, and confusion. Patients have prominent leptomeningeal enhancement. CSF findings are variable but may show a lymphocytic pleocytosis. Leptomeningeal biopsy may show perivascular inflammation. This may be associated with rheumatoid arthritis or idiopathic CNS vasculitis. It is essentially a diagnosis of exclusion when other infectious or inflammatory conditions are ruled out.

 Bruggemann N, Gottschalk S, Holl-Ulrich K, et al. Cranial pachymeningitis. Clin Exp Rheum. 2009; 27:S10–S13.