Antihypertensive therapy in pregnancy

A 35-year-old woman who is 15 weeks pregnant is referred for evaluation of chronic hypertension. She discontinued her antihypertensive regimen when she learned that she was pregnant.

On physical examination, heart rate is 90/min and blood pressure is 160/98 mm Hg. Cardiac and pulmonary examinations are normal.

Laboratory Studies
Blood urea nitrogen 6 mg/dL
Creatinine 0.6 mg/dL
Sodium 136 meq/L
Potassium 3.7 meq/L
Bicarbonate 23 meq/L

Treatment with which of the following agents is most appropriate for this patient?
A Hydrochlorothiazide
B Labetalol
C Lisinopril
D Losartan

Answer and Critique (Correct Answer = B)


Key Point
Labetalol or methyldopa is the preferred treatment for chronic hypertension in pregnant patients.

The most appropriate treatment for this patient is labetalol therapy. This agent has been used extensively in pregnancy because of its combined α-and β-blocking properties. Methyldopa also has been used extensively in pregnancy and is one of the only agents in which long-term follow-up of infants exposed in utero has proved to be safe.

Diuretic agents may interfere with the normal physiologic volume expansion associated with pregnancy. Therefore, initiation of diuretic therapy during pregnancy usually is not recommended in the absence of renal insufficiency. However, if needed, patients with hypertension treated with chronic diuretic therapy before conception may continue treatment with these agents at lower doses. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are contraindicated in pregnancy because of adverse effects on fetal renal function, particularly after second- and third- trimester exposure. There is no clear association between these drugs and teratogenic effects after first-trimester exposure. However, avoidance of these drugs is indicated during all trimesters of pregnancy because of the risk for negative fetal outcomes.

Multidrug antihypertensive therapy

A 59-year-old black man is evaluated during a routine follow-up office visit. He has occasional headaches but has otherwise been well. He had an anterior myocardial infarction 18 months ago and has hypertension, compensated congestive heart failure, type 2 diabetes mellitus, dyslipidemia, and mild chronic renal insufficiency. He is compliant with therapy, which includes metoprolol, lisinopril, amlodipine, metformin, atorvastatin, and aspirin.

On physical examination, heart rate is 62/min and blood pressure is 142/88 mm Hg. BMI is 24. Jugular venous pressure is 6 cm H2O. Cardiac examination reveals a regular rhythm; normal S1 and S2; and no S3, S4, or murmurs. The lungs are clear. There is no edema.

Laboratory studies: serum creatinine, 1.3 mg/dL; LDL cholesterol, 68 mg/dL; and spot urine albumin–creatinine ratio, 45 mg/g.

Which of the following is the most appropriate next step in this patient's management?
A Add clonidine
B Add hydrochlorothiazide
C Discontinue metoprolol; add hydralazine and isosorbide mononitrate
D Measure 24-hour urine catecholamines
E Reevaluate blood pressure in 2 to 3 months

Answer and Critique (Correct Answer = B)

Key Points

* Multidrug antihypertensive therapy is often needed to achieve optimal blood pressure control in patients with diabetes mellitus.
* An ineffective multidrug antihypertensive regimen should be considered a failure only if it includes a diuretic.

The addition of hydrochlorothiazide to this patient's medication regimen is the most appropriate next step. Patients with concomitant diabetes mellitus and hypertension typically require multidrug therapy to achieve target blood pressure goal (<130/80 mm Hg in this patient). Because this patient also has mild chronic kidney disease (calculated creatinine clearance, 69 mL/min) with microalbuminuria, ischemic heart disease, and congestive heart failure, blood pressure control is imperative. Adding a diuretic to a multidrug antihypertensive regimen may help to achieve a patient's blood pressure goal, and a regimen is not considered ineffective until a diuretic has been included.

Hydrochlorothiazide is administered once daily and is inexpensive and effective. Black patients usually respond less predictably well to angiotensin-converting enzyme (ACE) inhibitors, but the addition of a diuretic can help to equalize the effectiveness of these agents to that of white patients. Multiple trials have shown that β-blockers and ACE inhibitors are indicated in this setting. These agents prevent the progression of diabetic nephropathy, improve survival in heart failure, and provide secondary prevention of the acute coronary syndrome. Routine questioning of the patient about compliance is indicated, because compliance with therapy is a significant problem in hypertension management.

Clonidine has more side effects than similar agents and is not vasculo- or renoprotective; therefore, it is not indicated until all first-line agents have been tried. Hydralazine combined with nitrates is used as an alternative to ACE inhibitors or angiotensin-receptor blockers in patients intolerant to both, and can be added to standard heart failure therapy in black patients with heart failure. Hydralazine and nitrates have not been shown to have the same cardioprotective properties as ACE inhibitors. Patients with diabetes typically require three to four antihypertensive drugs, and this patient's medication regimen should not raise suspicion for a secondary cause of hypertension, such as pheochromocytoma. Moreover, this patient has no additional signs or symptoms suggestive of pheochromocytoma. Measurement of 24-hour urine catecholamines is therefore not indicated. Reevaluation in 2 to 3 months is not appropriate because blood pressure control in this setting is imperative to prevent morbidity and mortality.

Targeted BP for DM and Renal Failure Patient

A 57-year-old woman is evaluated in the office for intermittent claudication of the left calf that she has had for 5 years. The symptoms reproducibly occur after she walks 100 yards and resolve after 5 minutes of rest. The patient has an 80-pack-year smoking history but no longer smokes; she also has hypertension, type 2 diabetes mellitus, hypercholesterolemia, and chronic stable angina. Her medications are atenolol, atorvastatin, lisinopril, low-dose aspirin, and glyburide.

On physical examination, the blood pressure is 142/94 mm Hg in both upper extremities, and heart rate is 66/min. Carotid artery pulsations are brisk, with a right carotid artery bruit. The lungs are clear. Cardiac examination discloses an S4. There is a left femoral artery bruit with absent pulses in the left foot and trace pulses in the right foot.

Which of the following is the maximum acceptable blood pressure limit in this patient?
A <140/90 mm Hg
B <140/85 mm Hg
C <130/90 mm Hg
D <130/80 mm Hg

Answer and Critique (Correct Answer = D)


Key Point
The target blood pressure for patients with diabetes mellitus or renal failure is <130/80 mm Hg.

Hypertension is an independent risk factor for peripheral artery disease, and current guidelines support aggressive blood pressure management. For the general population, a blood pressure target of <140/90 mm Hg is associated with a decrease in cardiovascular complications, and a target pressure of <130/80 mm Hg is indicated for patients with diabetes mellitus (such as this patient) or renal failure.
Bibliography

1. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560-72. [PMID: 12748199] [PubMed]

Hypertension associated with Sleep Apnea (Apnoea)

A 48-year-old man is evaluated in the office for poorly controlled hypertension. His blood pressure has been elevated for 12 years and remains between 150/105 mm Hg and 170/105 mm Hg despite the use of multiple medications. He also has poor exercise tolerance and fatigue and often falls asleep in the afternoon. Medications are atenolol, amlodipine, and hydrochlorothiazide.

On physical examination, blood pressure is 168/110 mm Hg. He is obese (BMI 35) and appears plethoric. The remainder of the examination is normal.

Laboratory Studies
Creatinine 1.4 mg/dL
Sodium 140 meq/L
Potassium 3.9 meq/L
Bicarbonate 25 meq/L

Which of the following is the most likely cause of this patient's resistant hypertension?
A Pheochromocytoma
B Primary hyperaldosteronism
C Renovascular hypertension
D Sleep apnea syndrome

Answer and Critique (Correct Answer = D)


Key Point
Sleep apnea is associated with resistant hypertension and is particularly prevalent in obese patients.

Sleep apnea syndrome may contribute to resistant hypertension as well as to increased cardiovascular and cerebrovascular disease risk. Patients may have excessive fatigue and may fall asleep while driving or working. This condition has a higher prevalence in overweight men. The pathogenesis of sleep apnea syndrome is complex and linked to obesity, insulin resistance, and increased sodium retention. Several studies have shown that patients with sleep apnea syndrome have increased activity of the sympathetic nervous system, which also occurs in obesity. Coexistent insulin resistance and impaired glucose tolerance also may be present in these patients.

Renovascular hypertension may cause resistant hypertension but is less common than sleep apnea. In addition, the patient's age, obesity, plethora, and daytime sleepiness are more suggestive of sleep apnea than renovascular hypertension. Atherosclerotic renovascular hypertension usually develops in older patients, whereas fibromuscular dysplasia of the renal arteries often presents in younger patients and is more common in women.

Primary hyperaldosteronism may be present in as many as 10% of patients with resistant hypertension and should be included in the differential diagnosis. However, this condition is less likely in a patient who takes hydrochlorothiazide and has a normal potassium level.

Pheochromocytoma is a rare form of hypertension mediated by excess catecholamines. This condition causes palpitations, diaphoresis, tremor, flushing, and headaches. Diagnosis of pheochromocytoma may be difficult, and the clinical manifestations vary significantly. This patient's presentation is not fully consistent with this condition, and sleep apnea is more likely because it is more common and more likely to be associated with obesity, plethora, and daytime sleepiness.
Bibliography

1. Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, Eckel RH; American Heart Association; Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2006;113:898-918. Epub 2005 Dec 27. [PMID: 16380542] [PubMed]

Hypertension progress in DM

A 52-year-old woman with type 2 diabetes mellitus, hyperlipidemia, and hypertension is evaluated during a routine office visit. She has a 30-pack-year smoking history. Her mother had diabetes and required hemodialysis. Medications are insulin, metoprolol, fosinopril, hydrochlorothiazide, atorvastatin, and low-dose aspirin.

On physical examination, blood pressure is 165/95 mm Hg. Retinal microaneurysms are noted on funduscopic examination. There is no jugular venous distention. The lungs are clear. Cardiac examination reveals a regular rhythm with an S4. There is bilateral pedal edema. The distal pulses are absent in both feet.

Laboratory Studies
Hemoglobin A1c 7.2%
Glucose 180 mg/dL
Creatinine 1.2 mg/dL
24-Hour urine protein excretion 1.8 g/24 h

Which of the following factors is most likely to cause this patient's chronic kidney disease to rapidly progress to end-stage renal disease?
A Cigarette smoking
B Poorly controlled diabetes mellitus
C Poorly controlled hypertension
D Proteinuria

Answer and Critique (Correct Answer = C)

Key Point
Reduction in blood pressure slows the progression of renal disease and the development of cardiovascular disease in patients with diabetes mellitus.

Poorly controlled diabetes mellitus or hypertension, proteinuria, and cigarette smoking are all risk factors for chronic kidney disease progression. However, treatment of hypertension is the cornerstone in preserving renal function in patients with diabetic nephropathy. Reduction in blood pressure has been shown to influence progression of renal disease and the development of cardiovascular disease in patients with diabetes. The goal of treatment of blood pressure in patients with both type 1 and type 2 diabetes mellitus is to maintain a blood pressure ≤130/80 mm Hg in the absence of significant proteinuria and ≤125/75 mm Hg if accompanied by a urine protein concentration >1 g/24 h. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers constitute first-line treatment of hypertension, even in patients with advanced diabetic nephropathy.

The beneficial effect of strict metabolic control of diabetes on the progression of advanced renal disease is less established than is strict control of blood pressure. Nevertheless, metabolic control should be improved in this setting in order to minimize the risk for metabolic, microvascular, and macrovascular complications of diabetes. Proteinuria is a well-recognized risk factor for the progression of renal disease, including diabetic nephropathy. Cigarette smoking has been shown to have significant detrimental effects on the kidney and may cause increased proteinuria and an accelerated decline in renal function. Nevertheless, uncontrolled hypertension is the major factor contributing to progressive renal failure.
Bibliography

1. Barnett A. Prevention of loss of renal function over time in patients with diabetic nephropathy. Am J Med. 2006;119:S40-7. [PMID: 16563947] [PubMed]

Resistance to antihypertensive therapy due to NSAIDs

An 80-year-old man is evaluated in the office during a routine examination. He has a history of hypertension, and chronic osteoarthritis was diagnosed 20 years ago. His hypertension has been well controlled on submaximal dosages of both atenolol and hydrochlorothiazide. Three months ago, he began taking ibuprofen.

On physical examination, heart rate is 60/min and blood pressure is 180/90 mm Hg without orthostatic changes. There is trace peripheral edema.

Laboratory Studies
Blood urea nitrogen 40 mg/dL
Creatinine 1.5 mg/dL
Sodium 134 meq/L
Potassium 4.9 meq/L

Which of the following treatment strategies is indicated for this patient?
A Add lisinopril
B Discontinue ibuprofen
C Increase the atenolol dose
D Increase the hydrochlorothiazide dose


Key Point
Nonsteroidal anti-inflammatory drug use is a common cause of resistance to antihypertensive therapy.

Answer and Critique (Correct Answer = B)
Discontinuation of ibuprofen is indicated for this patient. Nonsteroidal anti-inflammatory drugs (NSAIDs) frequently affect sodium excretion. However, these agents are routinely used by elderly patients, who are particularly vulnerable to the blood pressure–raising effects of these drugs because of the change in sodium excretion. Most elderly patients have musculoskeletal conditions that warrant some form of therapy, but long-term daily treatment with NSAIDs may not be necessary. Alternative treatment strategies, such as physical therapy or therapy with acetaminophen, are indicated in this setting.

Discontinuing this patient's NSAID therapy is an appropriate next step to try to decrease his blood pressure. This strategy should be attempted before increasing his current medications or adding new medications, particularly because NSAIDs may contribute to renal and electrolyte disorders when used concomitantly with angiotensin-converting enzyme inhibitors or when taken by volume-depleted patients.
Bibliography

1. Gaziano JM. Nonnarcotic analgesics and hypertension. Am J Cardiol. 2006;97:10-6. Epub 2006 Mar 30. [PMID: 16675317] [PubMed]

White Coat Hypertension

An 85-year-old woman is evaluated in the office for resistant hypertension. She has a long-standing history of hypertension that had been well controlled with β-blocker therapy. Her physician recently died, and results of blood pressure measurement performed in a new office have been high. Records from her previous physician show that office blood pressure measurements were always normal. She also has fatigue, weakness, and dizziness, particularly after standing up. She has been unable to tolerate angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, and dihydropyridine calcium antagonist therapy. Current medications are metoprolol, 50 mg/d, and hydrochlorothiazide, 25 mg/d.

On physical examination, heart rate is 60/min and blood pressure in the supine and standing positions is 170/70 mm Hg. The remainder of the examination is normal.

Serum creatinine is 0.8 mg/dL, blood urea nitrogen is 18 mg/dL, and serum potassium is 3.6 meq/L.

Which of the following is the most appropriate next step in this patient's management?
A Ambulatory blood pressure monitoring
B Discontinuation of metoprolol
C Increase in the hydrochlorothiazide dose to 50 mg/d
D Magnetic resonance angiography of the renal arteries

Answer and Critique (Correct Answer = A)


Key Point
In selected patients, ambulatory blood pressure monitoring can exclude white coat hypertension.
The most appropriate next step in this patient's management is ambulatory blood pressure monitoring. White coat hypertension due to this patient's anxiety regarding a new physician and medication change is highly possible, and ambulatory blood pressure monitoring would confirm this diagnosis. In addition, overtreatment of hypertension in elderly patients is associated with increased adverse effects of medication, particularly symptoms associated with hypotension. Moreover, this patient's fatigue, weakness, and dizziness suggest that she is already overmedicated. Although current blood pressure targets for the elderly have not been clearly defined, a systolic blood pressure ≤160 mm Hg in this population has been associated with better outcomes. Ambulatory blood pressure monitoring is useful in this setting to document the level of blood pressure control.

Performing magnetic resonance angiography would be premature in this patient. Renovascular hypertension is a possible cause of resistant hypertension in the elderly, but her symptoms are consistent with overmedication. In addition, her long-standing history of stable hypertension is consistent with primary or essential hypertension. Increasing her hydrochlorothiazide dose before excluding a white coat effect could lead to increased symptoms. Lower doses of medication are indicated for many elderly patients, and 50 mg/d of hydrochlorothiazide most likely will be poorly tolerated in this patient.

Discontinuation of metoprolol may be reasonable. However, because of her elevated office blood pressure measurements, this agent should be discontinued only after documenting that her blood pressure is adequately controlled.
Bibliography

1. Fisher M, Blackwell J, Saseen J. Clinical inquiries. What is the best way to identify patients with white-coat hypertension? J Fam Pract. 2005;54:549-50, 552. [PMID: 15939009] [PubMed]

Diuretics potentiate the blood pressure–lowering effects of ACE inhibitors and β-blockers

A 60-year-old man with type 2 diabetes mellitus, hypertension, and coronary artery disease is evaluated during a routine office visit. Medications are metformin, a β-blocker, an angiotensin-converting enzyme inhibitor, aspirin, and a statin.

On physical examination, blood pressure is repeatedly 160/90 mm Hg. There is evidence of early diabetic retinopathy.

Laboratory Studies
Blood urea nitrogen 15 mg/dL
Creatinine 1.1 mg/dL
Potassium 5.4 meq/L
Spot urine albumin–creatinine ratio 175 mg/g

Addition of which of the following agents is indicated to treat this patient's hypertension?
A An angiotensin receptor blocker
B An α-blocker
C A potassium-sparing diuretic
D A thiazide diuretic

Answer and Critique (Correct Answer = D)


Key Point
Diuretics potentiate the blood pressure–lowering effects of angiotensin-converting enzyme inhibitors and β-blockers.

Therapy with a thiazide diuretic is indicated for this patient. This patient has type 2 diabetes mellitus, coronary artery disease, possible early diabetic nephropathy, and inadequate blood pressure control. His current regimen of a β-blocker and angiotensin-converting enzyme inhibitor is appropriate for cardiovascular disease and target organ protection. The addition of a thiazide diuretic is likely to improve blood pressure control, which is indicated to prevent further progression of target organ damage.

The addition of an angiotensin receptor blocker or potassium-sparing diuretic may provide renal protection and additional blood pressure control but would likely further exacerbate his hyperkalemia. Therapy with α-blockers has not been shown to have particular advantages compared with use of the other agents listed and may not lower blood pressure sufficiently.

Hyperaldosteronism

Hyperaldosteronism

A 39-year-old man is evaluated in the office for a 6-year history of difficult-to-control hypertension. Initially, he was treated with hydrochlorothiazide, but within 1 week, he developed profound muscle weakness; follow-up potassium concentration was 2.1 meq/L. Hydrochlorothiazide was discontinued, and he has not been on a diuretic for 6 years. He has struggled with obesity throughout his life and has a 7-year history of type 2 diabetes mellitus. His current medications are lisinopril, diltiazem, pravastatin, metformin, glipizide, and aspirin.

On physical examination, his blood pressure is 189/92 mm Hg, heart rate is 87/min, and BMI is 32.8. There is no jugular venous distention, and his lungs are clear. Cardiac examination reveals an S4. He has no edema.

Laboratory Studies
Sodium 141 meq/L
Potassium 3.1 meq/L
Chloride 104 meq/L
Bicarbonate 33 meq/L
BUN 11 mg/dL
Creatinine 0.9 mg/dL

24 hour urine:
Sodium 90 meq
Potassium 57 meq
Free cortisol 36 µg/24 h (normal <55 µg/24 h)

Which of the following is the most likely cause of this patient's hypertension?
A Cushing's syndrome
B Essential hypertension
C Hyperaldosteronism
D Pheochromocytoma
E Renovascular hypertension



Key Points

* The diagnosis of primary hyperaldosteronism is made by showing increased autonomous aldosterone synthesis with suppression of the renin-angiotensin system.
* Primary hyperaldosteronism is diagnosed in as many as 50% of patients with unprovoked hypokalemia.

Answer and Critique (Correct Answer = C)
This hypertensive patient has unprovoked hypokalemia, and his high urine potassium level indicates excessive renal potassium losses (in the presence of ongoing hypokalemia, a urine potassium concentration >30 meq/24 h identifies excessive renal potassium loss). These findings make hyperaldosteronism the most likely diagnosis listed. Hyperaldosteronism is included in the differential diagnosis of hypertension and hypokalemia. Unprovoked hypokalemia is highly suggestive of hyperaldosteronism—primary hyperaldosteronism has been identified in as many as 50% of patients with unprovoked hypokalemia. Severe hypokalemia following administration of a non–potassium sparing diuretic also is suggestive of hyperaldosteronism. Some patients with primary hyperaldosteronism are persistently normokalemic; thus, screening is also indicated in patients with early-onset, severe hypertension or resistant hypertension.

The diagnosis of primary hyperaldosteronism is made by showing increased autonomous aldosterone synthesis with suppression of the renin-angiotensin system. Although this test can be performed under random conditions, accuracy is increased if the sample is obtained after hypokalemia has been corrected and, preferably, in the absence of drugs that alter the renin-aldosterone axis, such as spironolactone (the effects of spironolactone can last 2 to 3 weeks), other diuretics, β-blockers, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). For a diagnosis of primary hyperaldosteronism, the plasma aldosterone concentration should be >15 ng/dL and plasma renin activity should be <1.0 ng/mL/h.

Cushing's syndrome is a reasonable consideration for a patient with difficult-to-control hypertension, obesity, and diabetes. However, this patient's 24-hour urine free cortisol is normal, ruling out Cushing's syndrome. Essential hypertension is not associated with hypokalemia, renal potassium wasting, or metabolic alkalosis. These findings more strongly suggest hyperaldosteronism. Pheochromocytoma is a very rare neoplasm that is associated with paroxysmal or sustained hypertension; however, pheochromocytoma is not associated with hypokalemia, renal potassium wasting, or metabolic alkalosis, making pheochromocytoma unlikely in this patient. Renovascular hypertension is often associated with older age and signs of other peripheral vascular disease, such as carotid bruits, claudication, diminished pulses, and coronary artery disease. Although the physical examination may be normal in patients with renovascular hypertension, the presence of abdominal, femoral, or carotid bruits increases its pretest probability. Atherosclerotic renovascular disease may be associated with renal impairment (which may worsen with ACE inhibitor or ARB therapy), which is absent in this patient. Finally, renovascular hypertension is not associated with hypokalemia, renal potassium wasting, or metabolic alkalosis.
Bibliography

1. Bornstein SR, Stratakis CA, Chrousos GP. Adrenocortical tumors: recent advances in basic concepts and clinical management. Ann Intern Med. 1999;130:759-71. [PMID: 10357696] [PubMed]

Ankylosing Spondilitis

A 22-year-old man is evaluated in the office for a 12-month history of gradually worsening low back stiffness that is present for 2 hours after awakening in the morning. He has significant fatigue but no fever, chills, night sweats, or weight loss. He does not have pains in the peripheral joints but does have bilateral buttock pains throughout the day on sitting. One year ago, he also had a 2-week episode of uveitis of the right eye, which responded to corticosteroid eye drops.

On physical examination, vital signs are normal. He appears healthy but walks with a mild forward bending of his spine. Deep pressure and palpation of the lumbar spine in the midline and both sacroiliac joints elicits tenderness. Chest expansion in the fourth intercostal space is 2 cm (normal ≥5 cm), and he can only reach the midcalf region when attempting to touch his fingers to the floor.

On laboratory studies, hemoglobin is 12.5 g/dL, erythrocyte sedimentation rate is 85 mm/h, and C-reactive protein is 5 mg/dL. Anteroposterior radiograph of the pelvis and sacroiliac joints is shown




Which of the following is the most likely diagnosis?
A Ankylosing spondylitis
B Metastatic cancer
C Osteoarthritis
D Sacral fracture

ANSWER

This patient most likely has ankylosing spondylitis, a systemic inflammatory disorder that most commonly occurs in men and primarily involves the spine and sacroiliac joints. Ankylosing spondylitis should be considered in the following : patients <40 years of age, patients with insidious onset of chronic low-back pain and stiffness of >3 months' duration; and those with low-back pain and stiffness that worsen at night or after prolonged rest or physical inactivity and are alleviated with physical activity or a hot shower. Within 6 to 12 months after disease onset, sacroiliac joint damage occurs and is manifested by narrowing and erosions, as seen on this patient's radiograph. The earliest finding is fuzziness and irregularity of the sacroiliac articular surface. Ankylosing spondylitis is later associated with subchondral sclerosis. These findings are first detected and are more marked on the iliac side of the joint. The erosion of the joint surface can cause erosions in and irregularity (serration) of the subchondral bone. The concomitant pseudo-widening of the joint space later leads to gradual joint space narrowing. The inflammatory process results in healing and bone formation that ultimately bring about fusion of the sacroiliac joints. Inflammatory changes also begin in the T12–L1 region of the spine and eventually lead to ossification of the outer fibers of the annulus fibrosis and the development of syndesmophytes. In the most severe cases of ankylosing spondylitis, “bamboo spine” develops, which is associated with soft tissue and bony changes that reflect this condition's inflammatory and calcifying nature.

Sacral fracture usually occurs in patients with osteoporosis and is triggered by seemingly minor episodes of trauma. Osteoarthritis of the spine or sacroiliac joints is common in older patients and is manifested by spur formation originating in the corners of the vertebrae and disk-space narrowing. In addition, pain in osteoarthritis, as well as mechanical back pain, is alleviated by a night of rest and worsens as the day progresses; conversely, low back pain in ankylosing spondylitis occurs because of inflammation and is therefore worse in the morning and is alleviated as the day progresses. Cancer of the spine or pelvis most often occurs in older patients because of metastatic disease and would be unusual in an otherwise healthy 22-year-old man. Furthermore, metastatic disease is associated with severe pain during the day and night. Imaging studies in this setting typically reveal lytic or blastic lesions.


Key Point
Consider ankylosing spondylitis in patients <40 years with insidious onset of chronic low-back pain and stiffness of >3 months' duration and low-back pain and stiffness that worsen at night or after prolonged rest or physical inactivity.

Spinal cord compression due to epidural metastasis

A 64-year-old woman is evaluated in the emergency department for a 4-day history of progressive bilateral leg weakness and numbness and a 1-day history of urinary incontinence. She has also had increasingly severe midback pain for the past 2 months. She has a history of breast cancer diagnosed 2 years ago and treated with surgery and local radiation therapy. Her only current medication is tamoxifen.

Physical examination shows normal mental status and cranial nerves. Strength in the arms is normal. The legs are diffusely weak, 3/5 proximally and 4/5 distally. Sensory examination shows diminished pinprick sensation from the nipples downward; vibratory sense is severely diminished in the feet. Reflexes are 2+ in the biceps and triceps and 3+ in the knees and ankles. An extensor plantar response is present bilaterally. Anal sphincter tone is diminished.

Which of the following is the most appropriate diagnostic study at this time?
A CT scan of the lumbar spine
B Electromyography and nerve conduction studies
C MRI of the brain
D MRI of the entire spine
E Plain radiographs of the entire spine


ANSWER

This patient has bilateral weakness and upper motor neuron signs in the legs, sensory loss below the T4 level, and sphincter dysfunction; there are no signs or symptoms of brain or brainstem dysfunction. These findings are consistent with a spinal cord process. Given her history of breast cancer, metastatic spinal cord compression from an epidural metastasis is most likely and represents a neurologic emergency that must be excluded by urgent imaging. Although the distribution of pain and the sensory level suggest that the lesion is at the thoracic level, MRI of her entire spine is most appropriate because sensory levels can be unreliable for localizing the site of an epidural tumor. In addition, patients with a metastatic epidural tumor can have multiple sites of disease in the spine. MRI gives excellent images of both the spinal cord and the vertebrae, whereas CT does not adequately show the substance of the spinal cord and epidural region, making MRI the modality of choice in this patient.

CT scan of the lumbar spine is not an appropriate imaging choice in this patient. Because the spinal cord ends at around the L1 vertebral body, the spinal cord would not be visualized if imaging of the lumbar spine alone is performed. Plain radiographs of the spine can visualize some bony metastases and fractures but are not sensitive for the site of cord compression and do not image the spinal cord. Electromyography and nerve conduction studies are helpful in diagnosing peripheral nerve and muscle diseases but have no role in the evaluation of spinal cord disorders. MRI of the brain may be needed to assess for asymptomatic brain metastases but is not as urgent as spine imaging.


Key Point
Spinal cord compression due to epidural metastasis is a neurologic emergency for which urgent MRI of the entire spine is appropriate.

Omega 3

Acute nonspecific low back pain

A 48-year-old man is evaluated in the office for back pain of 1 month's duration. He describes the pain as an ache that has been slowly worsening and is only partially relieved with acetaminophen. He is most comfortable lying down and least comfortable sitting or moving. He has not had any recent trauma or previous back pain. He has not had weight loss, fever, chills, numbness or weakness in his legs, or problems with bowel or bladder function. His only other medical problems are hypertension and osteoarthritis of the knees, for which he takes hydrochlorothiazide and acetaminophen, with occasional ibuprofen.

On physical examination, vital signs, including temperature, are normal. He has mild lumbar paravertebral tenderness and spasm. Neurologic examination, including muscle strength, deep tendon reflexes, and sensation, is normal. The straight-leg-raising test is normal.

Complete blood count and metabolic panel performed in the office 3 months ago were normal.

Which of the following is the best initial management plan for this patient?
A Analgesics and strict bed rest
B CT scan of the lumbosacral spine
C MRI of the lumbosacral spine
D Physical therapy
E Symptomatic treatment


ANSWER

This patient should do well with symptomatic treatment alone. Most acute nonspecific pain resolves over time without the need for treatment, and controlling pain while symptoms diminish on their own is the goal for most persons. A patient with back pain but at low risk for serious disease by history and physical examination does not need anything other than simple analgesics and continued activity. Some patients may benefit from the addition of moist heat.

Strict bed rest is associated with prolongation of symptoms and higher morbidity. A systematic review of bed rest for low back pain and sciatica showed that advice to continue normal activities was more beneficial than bed rest. The need for obtaining plain radiographs of the spine can be determined on the basis of the history and physical examination. More sophisticated imaging is most useful when the pretest probability of underlying serious disease is high. Diagnostic imaging techniques are indicated in individuals with “red flags” for serious underlying disease, including fever, chills, weight loss, history of malignancy, injection drug use, trauma, or indolent course. Some authorities recommend radiographic imaging of patients >50 years of age with low back pain because of the increased incidence of malignancy, compression fractures, and spinal stenosis in this age group. Physical therapy is an appropriate adjuvant but is not an appropriate initial treatment. Clinical trial evidence has shown that beginning back exercises immediately actually delays recovery.


Key Points

* Most acute nonspecific low back pain resolves over time without the need for treatment.
* Diagnostic imaging is indicated for individuals with “red flag” signs or symptoms for serious disease, including fever, chills, weight loss, history of malignancy, injection drug use, trauma, or indolent course.

omega 3

Vitamin C and Gout, A study

Vitamin C and Gout, A study

Men with a higher intake of vitamin C from food or supplements have a lower risk of developing gout, say researchers.

"Vitamin C intake may provide a useful option in the prevention of gout," Dr Hyon Choi and colleagues at the University of British Columbia in Vancouver say in a paper published in the Archives of Internal Medicine.

Gout is a form of arthritis from uric acid build-up that causes inflamed joints, typically in extremities such as toes, ankles and hands.

Sufferers are typically men age 40 and older, although it is known to also strike women.

Gout can lead to permanent joint damage and is linked to alcohol abuse, obesity, high blood pressure and a diet heavy in meat.

The research team found vitamin C appears to lower the levels of uric acid in the blood.

Lower risk

The study followed nearly 47,000 US men from 1986 to 2006 for a variety of health issues. Every four years, the men completed a dietary questionnaire, and their vitamin C intake through food and supplements was computed. During the study period 1317 men developed gout.

The researchers found that every 500 milligram increase of daily vitamin C intake produced a 17% decrease in the risk for gout.

Among the men studied those with daily intake of 1500 supplemental milligrams a day had a 45% lower risk of gout than those who took in less than 250 milligrams a day, says Choi.

An orange has about 70 milligrams of vitamin C - higher concentrations come in pill form.

Vitamin C may affect reabsorption of uric acid by the kidneys, increase the speed at which the kidneys work or protect against inflammation, all of which may reduce gout risk, the authors note.

But before stocking up on vitamin C, gout sufferers are reminded not to over do it.

The Australian National Health and Medical Research Council suggest adults should not consume more than 1000 milligrams of vitamin C each day.

Previous research has also linked fructose with an increased risk of gout. A 2008 study in the British Medical Journal found that two glasses of fruit juice a day, was a stronger risk factor than alcohol, and similar to meat and obesity.

Is human brain lost in space

Is human brain lost in space

The limitations of the human brain mean some of the biggest mysteries of the universe may never be solved, a top scientist has claimed.

According to the President of the Royal Society Lord Martin Rees, questions about the big bang and the existence of parallel universes may be never resolved because of the built-in limitations of mankind. He said that a true fundamental theory of the universe may exist, but could be just too hard for human brains to grasp.

Just as a fish may be barely aware of the medium in which it lives and swims, so the microstructure of empty space could be far too complex for unaided human brains.

His prediction was prompted by the failure of scientists to reconcile the forces that govern the behaviour of the cosmos with those that rule the micro world of atoms and particles.

While Einstein used mathematical calculations to build his 1915 theory of general relativity and 20th-century physicists devised quantum theory, no scientists has since found the tools to unify the two.

"Some aspects of reality, a unified theory of physics or a full understanding of consciousness, might elude us simply because they are beyond human brains, just as surely as Einstein ideas would baffle a chimp, "Rees said.

The royal astronomer said, "There are powerful reasons to suspect that space has a grainy structure, but on a scale a trillion trillion times smaller than atoms. Solving how this might work is crucial for 21st-century science."

Why Girls Can't Stop Stressing

Girls Can't Stop Stressing

Women may be more prone to emotional stress than men because of heir brain chemistry. US researchers found females were more sensitive to low levels of a key stress hormone called corticotropine-releasing factor.

A study of rats undergoing a swim stress test showed female animals had neurons that were more sensitive to CRF.

It was also found that stressed male rats adapted by making themselves less responsive to the hormone, but females didn't. The same signaling pathway is known to play a role in humans.

This may help to explain why women are twice as vulnerable as men to stress-related disorders.