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Teaching topics from the New England Journal of Medicine - Vol. 360, No. 16, April 16, 2009

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THIS WEEK'S TEACHING TOPICS 1.  Molar Pregnancy:  What is the difference between a complete and a partial mole? Is there a risk for persistent neoplasia after a molar pregnancy? Clinical Pearls | Morning Report Questions 2.  Case: Man with Migraine, Aphasia, and Hemiparesis:  What is the “misdiagnosis rate” of multiple sclerosis? What can cause multifocal white-matter lesions? Clinical Pearls | Morning Report Question 3.  Valsartan and Atrial Fibrillation:  What is the most common cardiac arrhythmia? What role does cardiac remodeling play in the recurrence of atrial fibrillation? Clinical Pearl | Morning Report Questions also in this e-mail: Images in Clinical Medicine Image Challenge Audio Videos in Clinical Medicine Featured Job of the Week Printer Friendly

Quote of the Week “ . . . the risk of major congenital malformations is two to four times as high with the use of valproate as with the use of other antiepileptic drugs such as carbamazepine and lamotrigine.” T. Tomson, Editorial, “Which Drug for the Pregnant Woman with Epilepsy?” top

TEACHING TOPIC 1. Molar Pregnancy CLINICAL PRACTICE, Molar Pregnancy, R.S. Berkowitz and D.P. Goldstein, Extract | Full Text | PDF | PPT Slide Set | Audio A healthy 37-year-old woman presents at 10 weeks of pregnancy with vaginal bleeding. Physical examination shows that the uterine size is appropriate for gestational age. The serum human chorionic gonadotropin (hCG) level is 22,000 mIU per milliliter. Ultrasonography does not show an identifiable heartbeat. The patient undergoes evacuation of the uterus; pathological examination indicates a complete molar pregnancy. How should this case be managed? top Clinical Pearls  Complete Mole versus Missed Abortion Ultrasonographic findings that do not include the characteristics of a molar pregnancy are usually presumed to be a missed abortion. An elevated hCG level at the time of ultrasonographic examination may help to distinguish an early complete mole from a missed abortion. However, a definitive diagnosis requires that a pathologist perform microscopic examination of tissue removed during uterine evacuation. Table 1. Chromosomal and Histopathological Features of Complete and Partial Moles.  hCG Testing after Molar Pregnancy After evacuation, serial hCG levels should be monitored in patients with either a complete or partial molar pregnancy in order to facilitate the early detection of persistent gestational trophoblastic neoplasia. To ensure that the patient has a complete, sustained remission, hCG tests are often performed weekly until levels have been undetectable (<5 mIU per milliliter) for 3 weeks, with subsequent monthly testing until levels have been undetectable for 6 months. top Morning Report Questions Q: Molar pregnancy comprises two distinct entities: partial and complete moles. What is the difference between the two? A: Complete moles have no identifiable embryonic or fetal tissues. Complete moles usually have a 46,XX karyotype, and the molar chromosomes are entirely from the father. Most complete moles are homozygous and appear to arise from an anuclear (“empty”) ovum that has been fertilized by a haploid (23X) sperm, which then replicates its own chromosomes. Partial moles can have identifiable fetal or embryonic tissues. Partial moles usually have a triploid karyotype that develops after the fertilization of an apparently normal ovum by two spermatozoa. When fetuses with partial moles are identified, they can have the congenital anomalies associated with triploidy, such as syndactyly and cleft lip. Levels of hCG tend to be higher (greater than 100,000 mIU per milliliter before evacuation) in the complete moles as compared to the partial moles. Q: Is there a risk for persistent neoplasia after a molar pregnancy? A: Yes. The criteria for the diagnosis of persistent neoplasia after molar pregnancy, as defined by the International Federation of Obstetrics and Gynecology, are serum hCG levels that do not return to normal range after evacuation, evidence of metastasis, and a pathological diagnosis of choriocarcinoma, any one of which establishes the diagnosis of persistent neoplasia. The incidence of gestational trophoblastic neoplasia after a complete molar pregnancy in the United States has been reported to be 18 to 29%. After a partial molar pregnancy the reported incidence ranges from 0 to 11%. top TEACHING TOPIC 2. Case: Man with Migraine, Aphasia, and Hemiparesis CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL, Case 12-2009: A 46-Year-Old Man with Migraine, Aphasia, and Hemiparesis and Similarly Affected Family Members, S.D. Brass and Others, Extract | Full Text | PDF | PPT Slide Set A 46-year-old man presented to the hospital with migraine headache and recurrent acute neurologic events over the past four years. Examination revealed cognitive changes, aphasia, and hemiparesis. His two brothers had been diagnosed with multiple sclerosis. Neuroimaging of the patient's brain revealed multifocal abnormalities in the basal ganglia and white matter. What is the differential diagnosis? top Clinical Pearls  Differential Diagnosis In addition to multiple sclerosis, the differential diagnosis in this patient with recurrent neurologic events includes small-vessel vasculitides, as well as other pathologic processes that could result in deep infarcts, such as hypercoagulable states, and inheritable or drug-induced small-vessel arteriopathies. Diseases that present with multifocal white-matter lesions include infectious diseases such as Lyme disease, HIV encephalitis, progressive multifocal leukoencephalopathy, and neurosyphilis; metabolic conditions such as vitamin B12 deficiency; toxic leukoencephalopathy; and inflammatory and immunologic diseases such as Behçet's disease, antiphospholipid-antibody syndrome, and neurosarcoidosis.  Multiple Sclerosis Multiple sclerosis is a challenging diagnosis to make and is associated with a misdiagnosis rate of 5 to 10%. The diagnosis relies on the presence of disseminated lesions in the central nervous system without findings that actually explain the disease process. MRI of the brain and spine, cerebrospinal fluid examination, and tests of visual evoked potentials may also help confirm the diagnosis. The patient most likely does not have multiple sclerosis if there is a lack of optic-nerve involvement and sensory symptoms on examination, or if there is predominant gray-matter involvement and sparing of the corpus callosum on MRI. Normal results on testing of the visual evoked potentials, the absence of oligoclonal bands, and a normal IgG index on cerebrospinal fluid examination might also indicate other diseases that could mimic multiple sclerosis. Table 1. Red Flags When Making a Diagnosis of Multiple Sclerosis. top Morning Report Question Q: What is homocystinuria and how might it manifest in the central nervous system? A: Homocystinuria is an autosomal recessive disease caused by mutations in one of four genes that are involved in methionine metabolism. The classic form is caused by mutations in the CBS gene, which encodes cystathionine β-synthase. Accelerated atherosclerosis, large-vessel and small-vessel ischemic infarcts, and extensive white-matter lesions may be seen. top TEACHING TOPIC 3. Valsartan and Atrial Fibrillation ORIGINAL ARTICLE, Valsartan for Prevention of Recurrent Atrial Fibrillation, The GISSI-AF Investigators, Abstract | Full Text | PDF | PPT Slide Set EDITORIAL, Angiotensin-Receptor Blockers for Prevention of Atrial Fibrillation — A Matter of Timing or Target?, A.M. Gillis, Extract | Full Text | PDF In a prospective, randomized trial, 1442 patients with a history of atrial fibrillation associated with cardiovascular disease, diabetes, or left atrial enlargement were assigned to receive either valsartan, an angiotensin II–receptor blocker, or placebo. At one year, there was no difference between the groups in the rate of either a first recurrence or multiple recurrences of atrial fibrillation. “Valsartan and possibly other ARBs do not prevent the recurrence of atrial fibrillation in this patient population.”  A.M. Gillis, Editorial, “Angiotensin-Receptor Blockers for Prevention of Atrial Fibrillation — A Matter of Timing or Target?” Figure 1. Kaplan–Meier Curves for the Time to the First Recurrence of Atrial Fibrillation. top Clinical Pearl  Atrial Fibrillation Some studies have shown that the recurrence of atrial fibrillation after cardioversion may be partially related to a biologic phenomenon known as cardiac remodeling, in which the electrical, mechanical, and structural properties of atrial tissue and cardiac cells are progressively and irreversibly altered, creating a more favorable substrate for atrial fibrillation. The renin–angiotensin–aldosterone system plays a role in atrial remodeling. Previous studies have suggested that ACE inhibitors and ARBs may have a beneficial effect on either new-onset atrial fibrillation or recurrent atrial fibrillation. top Morning Report Questions Q: What is the most common cardiac arrhythmia? A: Atrial fibrillation is the most common cardiac arrhythmia. Q: What is the difference between primary and secondary prevention of atrial fibrillation? A: Primary prevention would be the prevention of new-onset atrial fibrillation, whereas secondary prevention would be the prevention of the recurrence of atrial fibrillation. top

	IMAGES IN CLINICAL MEDICINE				IMAGE CHALLENGE
	Keyhole Pupils Get PowerPoint Slide Prosthetic Mitral Valve with Partial Thrombosis Get PowerPoint Slide MORE IMAGES				Question: What is the diagnosis? Check Your Answer 1. Epidermolysis bullosa 2. Hereditary hemorrhagic telangiectasia 3. Neurofibromatosis 4. Peutz-Jeghers syndrome 5. Scleroderma ABOUT THE IMAGE CHALLENGE
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	AUDIO				VIDEOS IN CLINICAL MEDICINE
	Listen to this week's Audio Summary Recent Interviews Anthony Fauci on the challenges and prospects of an HIV vaccine Wafaa El-Sadr on the successes and shortcomings of PEPFAR's efforts to address the HIV epidemic in the developing world Allan Brandt discusses the provisions, benefits, and criticisms of legislation that would grant the FDA regulatory authority over tobacco products MORE INTERVIEWS Recent Clinical Practice Molar Pregnancy Evaluation and Management of Enuresis MORE CLINICAL PRACTICE				Blood-Pressure Measurement Basic Splinting Techniques Peripheral Intravenous Cannulation Umbilical Vascular Catheterization MORE VIDEOS
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