Breast Cancer Prevention

Case Presentation

A 45-year-old female presents to your primary care office two days after learning that her 53-year-old sister has recently been diagnosed with breast cancer. She is distraught and asks you how common this is.

1. Regarding the incidence of breast cancer in the United States, which of the following is NOT true?

1. The cumulative risk for a woman being diagnosed with breast cancer by age 90 is approximately one in eight (12.5%).
2. Breast cancer is the most frequently diagnosed non-skin malignancy in U.S. women in 2011.
3. Only lung cancer is a larger cause of cancer mortality in women.
4. Approximately 20,000 new cases of breast cancer in men will have been diagnosed in 2011.
5. Data from the Surveillance, Epidemiology, and End Results Program show a decrease in breast cancer mortality of 1.9% per year from 1998 to 2007.

d. Correct.

Breast cancer is the most frequently diagnosed non-skin malignancy in U.S. women, and one in eight women will be diagnosed with breast cancer by age 90. Breast cancer will kill almost 40,000 women in 2011, and is second only to lung cancer as a cause of cancer mortality. Data from SEER has shown a 1.9% annual drop in breast cancer mortality.¹ It is estimated that 2,140 new cases of male breast cancer will have been diagnosed in 2011.²


Your patient mentions that her sister “may have had a drinking problem,” but states that she herself only drinks on weekends.

2. Regarding alcohol consumption and breast cancer risk, which of the following is true?

1. Randomized clinical trials have shown a causative effect from alcohol to the development of breast cancer.
2. The relative risk conferred by alcohol consumption does not differ based on the amount of alcohol consumed.
3. Drinking 3-6 glasses of wine per week has been shown to increase a woman’s risk of breast cancer by 15%.
4. Alcohol consumption between the ages of 18 and 40 does not appear to affect breast cancer risk if alcohol intake decreases after age 40.
5. Binge drinking has no relationship to future breast cancer risk.

c. Correct.
Data regarding alcohol intake and breast cancer risk comes from case-control, cohort, and observational studies. A British meta-analysis of 53 case-control and cohort studies showed a relative risk of breast cancer of 1.32 (95% CI, 1.19-1.45; P<.001) for women consuming 35g-44g of alcohol per day and 1.46 (95% CI, 1.33-1.61; P<.001) for those consuming at least 45g of alcohol per day. The relative risk of breast cancer increases by about 7% for each 10g (one drink) consumed per day.¹
Chen et al. have recently published results from the Nurses’ Health Study that included 105,986 patients from 1980-2008. With 2.4 million person-years of follow up, they have shown that even moderate drinking (3-6 glasses of wine per week) is associated with a 15% increased risk of breast cancer later in life. After controlling for cumulative alcohol intake, binge drinking was also associated with increased breast cancer risk. Alcohol intake both earlier and later in adult life was independently associated with risk.³





Your patient has a BMI of 30.

3. Which is the STRONGEST obesity-related predictor of breast cancer risk in postmenopausal women who do not take hormone replacement therapy?

1. Body weight.
2. Body mass index (BMI) at age 50.
3. Maximum BMI.
4. Postmenopausal weight change.
5. Waist and hip circumferences.

a. Correct.

A WHI observational study observed 85,917 women aged 50 to 79 years and collected information on weight history as well as known risk factors for breast cancer development. Among women who never used hormone replacement, increased breast cancer risk was associated with all of the following: increased body weight, BMI at study entry, BMI at age 50, maximum BMI, adult and postmenopausal weight changes, and waist and hip circumference. Body weight alone was the strongest predictor, with a RR of 2.85 (95% CI, 1.81-4.49) for women weighing more than 82.2kg compared to those weighing less than 58.7kg.⁴ It is uncertain, however, whether reducing weight would decrease a woman’s risk of developing breast cancer.¹


While collecting your patient’s obstetrical history, you learn that she has had three children but did not breastfeed more than a few months for each. She asks if this means she will get breast cancer.

4. Regarding breastfeeding and breast cancer risk, which of the following is true?

1. The duration of breast-feeding for the first child has no impact on the risk of the mother subsequently developing breast cancer.
2. Twelve months of breast-feeding is estimated to confer a 4% reduction in the lifetime risk of breast cancer for the mother.
3. In the year 2000, less than 50% of babies born in the United States were ever breast-fed.
4. The number of children breast-fed has no impact on risk reduction for breast cancer in the mother

b. Correct.

As early as 1926, it was proposed that a breast never used for lactation is more likely to become cancerous. The overall evidence from case-control and cohort studies supports a reduction in risk with longer duration of breast-feeding, but the findings have varied substantially in the level of risk reduction. A pooled analysis from almost 50 studies in 30 countries reported an overall 4% reduction in risk per 12 months of breast-feeding for all parous women. It is estimated that if women in developed countries had the number of births and lifetime duration of breast-feeding as women in developing countries, the incidence of breast cancer could be reduced by 60%. In the United States in the year 2000 more than 60% of infants were ever breast fed, but only 27% were receiving breast milk at 6 months of age.^1,5




Your patient also tells you that she was a “late bloomer” and did not experience menarche until age 16. She wonders if this means something is “wrong with her hormones.”

5. Regarding endogenous hormone exposure and the risk of breast cancer, which of the following is NOT true?

1. Ovarian ablation may reduce the risk of breast cancer by as much as 75%.
2. White women who experience a first full term pregnancy before 20 years of age were half as likely to develop breast cancer as nulliparous women or women who have their first full-term pregnancy at age 35 years or older.
3. Women who experience menarche at age 11 years or younger had about a 50% greater chance of developing breast cancer than do women who experience menarche at age 14 years or older.
4. In the Nurses Health Study, the associations between age at first birth, menarche, and menopause and the development of breast cancer were observed only in women without a family history of breast cancer in a mother or sister.

c. Correct.

Ovarian ablation may reduce breast cancer risk by as much as 75% depending on age, weight, and parity, with the greatest reduction in young, thin, nulliparous women. Earlier pregnancy also reduced breast cancer risk: white women who experienced a first full term pregnancy before age 20 were half as likely to develop breast cancer as nulliparous women or those who had their first full term pregnancy at age 35 or older. There may be racial differences in these risk factors in African American women, which are currently being further explored. Another study showed that women who experience menarche at age 11 or younger were about 20% more likely to develop breast cancer than those who experienced menarche at age 14 or older. However, in the Nurses Health Study, the associations between age at first birth, menarche, menopause, and the development of breast cancer were observed only among women without a first-degree relative with breast cancer.¹




During the review of systems, it becomes apparent that your patient has been experiencing some menopausal symptoms, and asks if something “safe” can be prescribed to help with her severe unrelenting hot flushes and night sweats.

6. Regarding the Women’s Health Initiative combined estrogen-progestin hormone replacement therapy (HRT) trial, which of the following is FALSE?

1. It was stopped early after showing an increased breast cancer risk with combined estrogen-progestin therapy
2. The excess risk was observed in all subgroups of women for both invasive and in situ breast cancer.
3. Patients who developed cancer on combined HRT showed trends towards larger tumor size and higher incidence of lymph node metastases.
4. Extended follow up at 14 years showed increased breast cancer specific mortality.

b. Correct.

The WHI combined estrogen-progesterone trial included women aged 50-79 years who had intact uteri. They were randomly assigned to receive combined conjugated estrogen and continuous progestin (8,506 women) or were assigned to receive placebo (8,102) women. Breast cancer risk was increased (Hazard Ratio 1.24; 95% CI, 1.02-1.50) in the combined HRT group, causing early termination of the study. The excess risk was observed in invasive breast cancer, but not in situ cancers. Patients who did develop cancer in the combined HRT group showed trends towards both larger tumor size and higher incidence of lymph node positivity. An extended follow up at 14 years showed an even larger difference in breast cancer incidence in the HRT group and an increased breast cancer specific mortality (HR 1.95; 95% CI, 1.0-4.04; P=.049).^1,6



After explaining the increased risks of combined HRT, she asks "My sister takes only estrogen after her hysterectomy. What is her risk?”

7. Regarding the Women’s Health Initiative Estrogen-Alone Trial, which of the following is TRUE?

1. It evaluated the use of estrogen-only HRT in women with intact uteri.
2. Estrogen-only preparations are safe in women who have had a hysterectomy as well as those who have intact uteri.
3. This trial was stopped early because of an increased risk of breast cancer in the HRT group.
4. The incidence of breast cancer was lower in the group receiving estrogen-only HRT at 6.8 years of follow up.
5. Over the extended follow up period (10.7 years), there were increased risks of coronary heart disease, deep vein thrombosis, stroke, hip fracture, and colorectal cancer.

d. Correct.

The Women’s Health Initiative Estrogen-Alone Trial was a randomized control only for women who had had a hysterectomy. This is because unopposed estrogen therapy increases the risk of uterine cancer. This trial was stopped early due to an increased risk of stroke in the HRT group and no evidence of benefit as measured by a global index of risks and benefits. After an average 6.8 years of follow-up, the incidence of breast cancer was slightly lower in the HRT group, but this difference was not statistically significant. (HR=.77; 95% CI, 0.59-1.01)¹ Over the extended follow up period of 10.7 years, the decreased risk of breast cancer persisted (HR=.75; 95% CI, 0.51-1.09) and there was neither an increased or decreased risk of coronary heart disease, DVT, stroke, hip fracture, or colorectal cancer between the estrogen only HRT group and placebo.⁷



Your patient’s sister was told that she would need to take tamoxifen to treat her breast cancer, and your patient has brought a printed web page discussing the various indications for tamoxifen.

8. Which of the following statements regarding the Breast Cancer Prevention Trial (BCPT, also known as NSABP P-1) is FALSE?

1. It was a randomized controlled trial that assigned 13,388 patients at elevated risk for breast cancer to receive tamoxifen 20mg daily for five years or placebo.
2. It was closed early after showing a 49% reduction in the incidence of breast cancer for the group receiving tamoxifen.
3. There was no reduction in the incidence of noninvasive breast cancers.
4. A reduction in fractures was observed in the tamoxifen treated group.
5. An increase in endometrial cancer and thrombotic events was noted in women aged 50 years and older.
6. No overall mortality benefit was seen for tamoxifen prevention after seven years of follow up.

c. Correct.

The BCPT (NSABP P-1) showed a reduction in the incidence of both invasive and noninvasive breast cancers. There were 31 cases of noninvasive cancers in the tamoxifen treated group versus 59 in the placebo group. All of the other above statements regarding the BCPT are correct.^1,8,9


She asks if you will prescribe tamoxifen for her.

9. Which of the following statements regarding management recommendations for chemoprevention of breast cancer is FALSE?

1. The Food and Drug administration has approved the use of tamoxifen for breast cancer risk reduction in women who are 35 years or older and have a 5-year risk of 1.66% or more as determined by the Gail model.
2. The American Society of Clinical Oncology Working Group has advised that patients with the risk of an average 60 year-old white North American female be offered tamoxifen chemoprevention.
3. Premenopausal women at increased risk for the development of breast cancer derive the greatest net benefit because of the absence of increased risks for either thromboembolic events or uterine cancer in this group.
4. Despite having been shown to offer a similar breast cancer risk reduction to tamoxifen, raloxifene has significant safety disadvantages compared to tamoxifen and is not currently recommended for chemoprevention.

d. Correct.

The FDA has approved tamoxifen for breast cancer risk reduction in women who are 35 years or older and have a 5 year risk of 1.66% or more as determined by the Gail model. (www.cancer.gov/bcrisktool) The American Society of Clinical Oncology Working Group has also advised offering tamoxifen to patients with a 1.66% 5-year risk, which is the risk of the average, 60 year-old white, North American female. However, the group (and others) has noted that the greatest clinical benefit is observed when tamoxifen was given to younger, premenopausal women, women without a uterus, and in women with a higher risk of breast cancer. Raloxifene 60mg orally daily for five years offers an acceptable and similarly effective alternative to tamoxifen for the reduction of breast cancer risk in high risk postmenopausal women and is associated with lower risks of both benign and malignant uterine events as well as significantly less thromboembolic toxicity.¹⁰


After referral to a medical breast specialist for risk calculation and consideration of tamoxifen chemoprevention, your patient asks if there is anything else she could take to reduce her risk.

10. Which of the following statements regarding diet and vitamins and breast cancer is FALSE?

1. In a randomized controlled trial as part of the WHI enrollment, the group that reduced fat intake by 10% for approximately 8 years of follow was shown to have a slightly lower incidence of invasive breast cancer.
2. Fruit and vegetable consumption has been linked to the prevention of breast cancer.
3. There are no specific micronutrients, including beta carotene, Vitamin E, folic acid, vitamin B6, or vitamin B12 that have been shown to reduce breast cancer risk.
4. Fenretinide is a Vitamin A analog that has been shown to reduce breast carcinogenesis in preclinical trials, but a randomized trial showed no significant differences in the incidence of breast cancer, nonbreast malignancies, or all-cause mortality.

b. Correct.

A randomized dietary modification study was undertaken among 48,835 women in the WHI study. The goal fat reduction was 20% but the intervention group was able to reduce fat consumption by 10% on average. At 8.1 years of follow up, the incidence of invasive breast cancer was slightly lower in the fat reduction group (HR 0.91, 95% CI, 0.83-1.01). A pooled analysis of eight cohort studies investigating fruit and vegetable consumption showed little evidence of a reduction in breast cancer based on increased fruit and vegetable consumption. No randomized trials have examined the effect of fruit and vegetable consumption on breast cancer.¹
Beta-carotene, Vitamin E, folic acid, vitamin B6, and vitamin B12 have all been investigated as supplements to reduce breast cancer risk. None of these have shown a reduction. Fenretinide is a Vitamin A analog that has been shown to reduce breast carcinogenesis in preclinical trials, but a phase III Italian randomized trial using a 5 year intervention with fenretinide versus no treatment showed no statistically significant differences in the incidence of breast cancer, nonbreast malignancies, or all-cause mortality.¹




Key Points

1. There may be no “safe” level of alcohol intake with regards to breast cancer risk. Even moderate alcohol consumption has been tied to an increased risk of breast cancer, although risk does increase with heavier and more frequent drinking.
2. Body weight, BMI, and adult weight changes have all been associated with an increased risk of breast cancer. A low fat diet may decrease the risk (likely by decreasing weight), but no other specific dietary modifications (fruits / vegetables, vitamins) have been conclusively shown to reduce risk.
3. In general, increased lifetime endogenous estrogen exposure (early menarche and late menopause) is associated with increased breast cancer risk, as is delayed childbirth, which is a worldwide trend.
4. Extended use of combined HRT (estrogen plus progesterone) is best avoided for breast cancer prevention.
5. Tamoxifen 20mg daily for five years is approved for breast cancer risk reduction in women who are 35 years or older and have a 5 year risk of 1.66% or more as determined by the Gail model. The greatest clinical benefit is observed when tamoxifen was given to younger, premenopausal women, women without a uterus, and in women with a higher risk of breast cancer. Raloxifene 60mg orally daily for five years offers an acceptable alternative to tamoxifen for the reduction of breast cancer risk in high risk postmenopausal women.

A Severe Headache in a Young Woman

An ambulance brings a 39-year-old woman complaining of a severe occipital headache and vomiting from her workplace to the emergency department (ED). She describes the headache as “the worst ever headache of my life” and states that it started suddenly, after a stressful situation at work. The intensity of the headache did not diminish after taking 200 mg of ibuprofen. She denies any head trauma, intense physical exertion, fever, changes in vision, photophobia, or any other associated symptoms (other than vomiting). She mentions that 2 days before presentation, she had a headache of similar intensity, but it only lasted a few seconds before resolving spontaneously. Her medical history is remarkable for 2 normal pregnancies with uncomplicated deliveries. She denies any prior surgeries, and her only medications are oral contraceptives, which she has taken for about 15 years. She works as a dressmaker and denies illicit drug use, tobacco use, or alcohol consumption. She does not recall any significant medical problems in her family history.

On physical examination, she is obese and appears her stated age. She is in mild distress due to pain. Her axillary temperature is 97.8°F (36.6°C). Her pulse is regular at 78 bpm, her blood pressure is 160/80 mm Hg (which she states is high for her), and her respiratory rate is 20 breaths/min. Her head is normal on inspection, without any areas of tenderness. The ears, nose, and throat are clear. Her pupils are both small at 2 mm, but they are reactive to light. Otherwise, the eyes appear normal, with normal extraocular movements and no photophobia or nystagmus. The fundi and optic discs appear normal. No masses are detected on examination of her neck, but significant nuchal rigidity is noted. The chest examination is normal, with lungs clear to auscultation bilaterally and normal respiratory effort. The heart sounds are also normal. Her abdomen is soft and nontender. The neurologic examination reveals that she is fully alert, oriented, and mildly anxious. Her cranial nerves are intact. Motor strength is symmetrical, with brisk and symmetric deep tendon reflexes without clonus. Cerebellar function and sensory systems are normal.

Laboratory analyses, including a complete blood count, metabolic panel, and urine analysis, are normal. A noncontrast cerebral computed tomography (CT) scan is performed (Figure 1).

Top of Form

Questions answered incorrectly will be highlighted.

What is the diagnosis?

Hint: The patient has no prior history of similar headaches.

Migraine headache

Subarachnoid hemorrhage

Meningitis

Vertebral artery dissection

Cerebral venous sinus thrombosis

Case discussion

The diagnosis of spontaneous subarachnoid hemorrhage (SAH) was made based on the hyperdensity seen in the subarachnoid space on the noncontrast-enhanced cerebral CT scan (Figure 2). Once the CT diagnosis was made, the other diagnoses in the differential above were effectively ruled out, as the likelihood of 2 simultaneous processes is very low. The history did not reveal significant head trauma, so it was concluded that this was a spontaneous (nontraumatic) SAH. After making the diagnosis and controlling the patient’s pain, urgent neurosurgical consultation was obtained.

Spontaneous SAH is a neurosurgical emergency and a life-threatening condition. It can progress to coma, permanent brain damage, and death. It is characterized by extravasation of blood into the subarachnoid space, most commonly from a berry aneurysm or other vascular malformation. The incidence of subarachnoid hemorrhage is 2-49 cases per 100,000 people per year internationally, and 10%-15% of patients die before reaching the hospital. People of African heritage are at higher risk than whites by a ratio of 2.1 to 1. Asians are also at higher risk, and the incidence of subarachnoid hemorrhage is higher in women. Other risk factors include polycystic kidney disease, lupus, Ehlers-Danlos syndrome, and tobacco use. The mean age of onset is 50 years.^[1,2]

The typical presentation of a nontraumatic SAH is marked by the sudden onset of a severe headache, which has been dubbed “thunderclap headache.”^[2] The rapid onset of the headache is the most important historical feature. Patients usually refer to an SAH as the worst headache of their life; however, patients presenting to an ED with headache of any etiology will often have the same complaint. Headache from SAH tends to be occipital in location. In patients with a prior history of cephalgia, headache from SAH is usually, but not always, described as different from prior headaches. Sentinel headaches are SAHs that do not cause catastrophic damage. If recognized, a sentinel headache provides an opportunity for intervention before a larger, more debilitating SAH occurs. Patients may also experience epileptic seizures, nausea or vomiting, neck stiffness, photophobia, and loss of consciousness. On physical examination, neurologic and vital-sign abnormalities may be present; these include cranial nerve signs, motor deficits, seizures, coma, ophthalmologic signs (papilledema, retinal hemorrhage), and mild-to-moderate blood pressure elevation.^[1] A history of headache prior to a fall or syncopal episode or an uncertain history of trauma should increase suspicion for spontaneous SAH.

The severity of an SAH is most commonly graded using the Hunt-Hess scale, as follows^[2]:

Unruptured aneurysm
Asymptomatic or minimal headache without neck rigidity
•  Moderate-to-severe headache, neck rigidity, cranial nerve palsy
Drowsy, confused, mild focal deficit
Stupor, moderate-to-severe deficit, hemiparesis
Deep coma, decerebrate rigidity, moribund

The differential diagnosis of SAH is very large. It includes encephalitis, meningitis, primary headaches (migraine, cluster headache), temporal arteritis, hypertensive encephalopathy, spontaneous intracerebral hemorrhage, ischemic stroke, transient ischemic attack, panic attack, craniocervical dissections, and cerebral venous sinus thrombosis, as well as other causes of headache.^[1]

The most useful initial diagnostic tool to confirm the diagnosis of SAH is a noncontrast brain CT scan, which shows the hyperdense collection of blood in the subarachnoid space. The sensitivity of CT scanning of the brain is considered to be 90%-95% within 24 hours of symptom onset, 80% at 3 days, and 50% at 1 week.^[1] In a recent study, high-resolution CT scanning was positive for SAH in all cases examined within 12 hours from the onset and in 93% of patients who presented within 24 hours of onset.^[3] Brain CT scan is also useful because it may demonstrate associated complications of SAH, such as hydrocephalus, ischemic strokes due to vasospasm, mass effect, and signs of impending herniation. A falsely negative CT scan may result if there is only a very small sentinel bleed. These patients will usually be Hunt-Hess grade 1, and they are also the patients with the best prognosis if they are diagnosed and treated before a catastrophic SAH. Other possible causes of a false-negative CT scan include a delay of more than 12 hours from symptom onset, anemia (with a hemoglobin < 10 g/dL), and movement artifacts. The clinician should always ask the radiologist if a careful review for blood in the interpeduncular cistern was performed. This area sits just posterior and thus dependent on the circle of Willis and, therefore, forms a natural “cup” that may collect just enough blood to be seen on CT when an SAH is very small.

The gold standard diagnostic test for SAH is a lumbar puncture (LP) with cerebrospinal fluid (CSF) analysis. An LP must be performed after a negative brain CT scan whenever there is a suspicion of SAH and no contraindications to the procedure. As opposed to CT scanning, the sensitivity of lumbar puncture for SAH initially improves as the time from onset increases. In addition, an important alternate diagnosis, such as meningitis or encephalitis, may be made. The most important CSF findings in SAH are consistently elevated red blood cell counts in 2 or more tubes, as well as xanthochromia, which is seen by 12 hours after the onset of bleeding. The opening pressure should be measured, as it is often elevated in cases of SAH. A false-negative LP may occur if the procedure is done too early, before enough time has elapsed for blood from the brain to circulate down into the lumbar area. Although it is not recommended that LP be delayed because of this reason, it is important to know that sensitivity decreases if the LP is performed before 12 hours from symptom onset. Fortunately, this is exactly the time frame in which the CT scan is most sensitive. In addition, LP loses sensitivity after 2 weeks from symptom onset.

Once the diagnosis of SAH has been confirmed either by CT or LP, medical stabilization should be instituted. This is followed by an urgent examination of the intracerebral blood vessel anatomy for early visualization of the bleeding source (if it exists), which most often is a berry aneurysm or arteriovenous malformation (AVM). Medical stabilization is aimed at preventing early complications, including brain edema, hydrocephalus, and rebleeding, as well as the late complication of vasospasm. Treatment options include bed rest with elevation of the head of the bed to 30 degrees, nimodipine (a calcium channel blocker to prevent vasospasm), seizure prophylaxis, antiemetics, analgesia, and labetalol or other agents as needed for blood pressure control.

Vascular malformations leading to SAH can be identified by conventional cerebral angiography, CT angiography, or by magnetic resonance angiography of the cerebral vasculature. Other indications for one of these tests would be if LP is not possible or is refused by the patient or if the work-up is negative but more than 2 weeks since symptom onset have passed. Some experts also recommend angiography in certain high-risk patients despite a negative CT and LP, such as those with polycystic kidney disease, Marfan syndrome, a family history of SAH, or suspicion for vascular dissection. The clinician should not recommend angiography in lieu of LP, however, because it is neither extremely sensitive nor specific for the diagnosis of SAH. Angiography is only 80%-90% sensitive for SAH.^[4] In addition, approximately 1%-2% of the population has an asymptomatic berry aneurysm.^[2] Unless they are large or have bled, these aneurysms do not require treatment. Making the diagnosis of berry aneurysm without an LP showing an SAH may lead to confusion about the best course of action or even to unnecessary surgery.

Digital-subtraction cerebral angiography is invasive, but it has a great sensitivity for showing vascular anatomy and current bleeding site, and to visualize other aneurysms or AVMs. Magnetic resonance angiography is noninvasive, but it has lower sensitivity for visualization of the intracerebral vessels, requires more time to perform the examination, has a greater risk of movement artifacts, and is more examiner-dependent. CT angiography has a similar sensitivity but exposes the patient to a greater dose of radiation and is also examiner-dependent.^[1] In 10%-20% of patients with SAH, there is no evident source of bleeding after imaging assessment of the cerebral vessels (nonaneurysmal SAH).^[4] The outcome of nonaneurysmal SAH is better than that of aneurysm rupture or AVM. Depending on the localization of the subarachnoid blood, there are 2 nonaneurysmal SAH patterns that mimic true aneurysmal rupture: perimesencephalic hemorrhage and “aneurysmal hemorrhage pattern.”^[5] When angiography is positive, early neurosurgical intervention with clipping, coiling, or glue injection into the vascular malformation improves the outcome of patients and decreases the risk of rebleeding (a major complication of SAH).

The patient in this case was diagnosed with a Hunt-Hess Scale grade 2 SAH based on her severe headache and the nuchal rigidity found on the physical examination. She was referred to the neurosurgical department after the CT scan results were evaluated. Urgent cerebral angiography was performed, which was negative for intracerebral aneurysm or AVM. Magnetic resonance angiography was performed the next day and was also negative. The patient remained in the neurosurgical department for close observation. She received intravenous fluids, nimodipine, analgesics, and laxatives. She was monitored for cerebral vasospasm by transcranial Doppler sonography and was kept on bed rest for the first 10 days of her admission, with progressive active mobilization thereafter. She developed mild, subclinical vasospasm on day 5 of hospitalization, which resolved completely afterward. She was transferred to the neurologic department for further conservative treatment on day 9 and discharged from the hospital on day 17. Her clinical condition improved continuously during her admission, with resolution of her headache, nuchal rigidity, and miosis and with no development of other neurologic signs during her observation. A CT scan performed 1 month later (Figure 3) showed complete absorption of the blood from the subarachnoid space, with no sign of hydrocephalus or other complications. At discharge, sexual abstinence was recommended for 6 weeks in order to decrease the chance of rebleeding. She was also counseled to avoid strenuous activity for the first 6 weeks after her discharge from the hospital. After 3 months, the patient’s clinical condition remained excellent.

Top of Form

Questions answered incorrectly will be highlighted.

You are seeing a patient with a severe headache and suspect a subarachnoid bleed. Which of the following historical features is most suggestive of subarachnoid hemorrhage

Sudden, rapid onset of headache

Vertigo

Associated vomiting

Fever

Frequent, similar headaches in the past

You are seeing a patient who presents with a thunderclap-type headache. Which of the following is the most useful initial diagnostic tool to evaluate for a subarachnoid hemorrhage

Brain CT scan with intravenous contrast

Noncontrast brain CT scan

Funduscopic examination of the retina

MRI of the brain