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Review Article
Mechanisms of Disease: Monogenic Mitochondrial Disorders
To function normally, human cells require energy in the form of ATP. In many cell types, ATP is primarily generated by mitochondria, which are also key players in other important cellular processes, such as adaptive thermogenesis, ion homeostasis, innate immune responses, production of reactive…
- March 22, 2012
- Koopman W.J.H., Willems P.H.G.M., Smeitink J.A.M.
- N Engl J Med 2012; 366:1132-1141
Rare monogenic disorders of mitochondria have shed light on mitochondrial function, and the development of therapeutic agents for these disorders may be applicable to more common sporadic diseases characterized by mitochondrial dysfunction.
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Editorial
Intramuscular versus Intravenous Benzodiazepines for Prehospital Treatment of Status Epilepticus
Acute seizures account for 1% of adult and 2% of pediatric emergency department visits, at an annual cost of $1 billion (in U.S. dollars). When seizures are prolonged or repetitive without recovery between episodes, the condition is termed status epilepticus, and it occurs in approximately 6% of…
- February 16, 2012
- Hirsch L.J.
- N Engl J Med 2012; 366:659-660
Acute seizures account for 1% of adult and 2% of pediatric emergency department visits, at an annual cost of $1 billion (in U.S. dollars).¹ When seizures are prolonged or repetitive without recovery between episodes, the condition is termed status ...
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Original Article
Intramuscular versus Intravenous Therapy for Prehospital Status Epilepticus
Early termination of prolonged epileptic seizures in response to intravenous administration of benzodiazepines by paramedics in the prehospital setting is associated with better patient outcomes. The randomized, controlled Prehospital Treatment of Status Epilepticus (PHTSE) trial (ClinicalTrials…
- February 16, 2012
- Silbergleit R., Durkalski V., Lowenstein D., et al.
- N Engl J Med 2012; 366:591-600
In this trial, subjects in status epilepticus were given either intramuscular midazolam or intravenous lorazepam by paramedics before arrival in the ER. Seizures were controlled in more subjects with midazolam, and midazolam was at least as safe and effective as lorazepam.
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Case Records of the Massachusetts General Hospital
Case 34-2011 — A 75-Year-Old Man with Memory Loss and Partial Seizures
Presentation of Case. A 75-year-old physician was seen in an outpatient office at this hospital because of memory loss and episodes of near-syncope. The patient had been generally well, except for mild and gradual memory loss, until 7 months earlier, when episodes of diffuse tingling and a…
- November 10, 2011
- Cash S.S., Larvie M., Dalmau J.
- N Engl J Med 2011; 365:1825-1833
A 75-year-old man was seen because of memory loss and episodes of near-syncope, with word-finding difficulty and unilateral twitching. MRI with contrast material revealed hyperintensity and mild expansion of the left hippocampus, without enhancement.
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Review Article
Current Concepts: Sudden, Unexpected Death in Epilepsy
Epilepsy is characterized by both recurrent seizures and clinical uncertainty. Paroxysmal symptoms unpredictably punctuate life. Although most people with epilepsy live full and productive lives, doctors may too readily assure patients that seizures "never hurt the brain" and "are never fatal."…
- November 10, 2011
- Devinsky O.
- N Engl J Med 2011; 365:1801-1811
- CME
The magnitude of the problem of sudden unexplained death in epilepsy is unrecognized in both the medical and lay communities. This review presents information on frequency, risk factors, and theories about mechanisms and recommends strategies for prevention and for patient education.
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Correspondence
“Bath Salts” Intoxication
To the Editor: The abuse of psychoactive "bath salts" (PABS) has become commonplace, and patients with PABS overdoses are presenting to emergency departments with increasing frequency. The primary ingredient of the synthetic designer drugs in these bath salts, which are not related to any hygiene…
- September 8, 2011
- N Engl J Med 2011; 365:967-968
- Free Full Text
This letter highlights recreational ingestion of bath salts containing methylenedioxypyrovalerone, a potent central nervous system stimulant. Intoxication that results in extreme sympathetic stimulation and profoundly alters mental status may be fatal.
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Review Article
Current Concepts: Drug-Resistant Epilepsy
Fifty million people in the world have epilepsy, and there are between 16 and 51 cases of new-onset epilepsy per 100,000 people every year. A community-based study in southern France estimated that up to 22.5% of patients with epilepsy have drug-resistant epilepsy. Patients with drug-resistant…
- September 8, 2011
- Kwan P., Schachter S.C., Brodie M.J.
- N Engl J Med 2011; 365:919-926
- CME
Nearly a quarter of patients with seizures have drug-resistant epilepsy. This review examines how this diagnosis should be established and how to recognize pseudoresistance. It explains possible mechanisms of drug-resistant epilepsy and presents treatment strategies.
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Case Records of the Massachusetts General Hospital
Case 26-2011 — A 7-Year-Old Boy with a Complex Cyst in the Kidney
Presentation of Case. A 7-year-old boy was seen in an outpatient clinic at this hospital because of a complex cyst in the kidney. The patient was born by vaginal delivery after an uncomplicated 38-week gestation. His birth weight was 3.04 kg. A diagnosis of tuberous sclerosis complex (TSC) was made…
- August 25, 2011
- Paul E., Thiele E.A., Shailam R., Rosales A.M., Sadow P.M.
- N Engl J Med 2011; 365:743-751
- CME
A 7-year-old boy with tuberous sclerosis complex was seen because of an increasingly complex cyst in the left kidney, seen on serial imaging studies. A diagnostic procedure was performed.
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Clinical Problem-Solving
A Sweet Source of Abdominal Pain
Foreword. In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information, sharing his or her reasoning with the reader (regular type). The authors' commentary follows. Stage. A 25-year-old woman presented to…
- May 5, 2011
- Rogal S.S., Ukomadu C., Levy B.D., Loscalzo J.
- N Engl J Med 2011; 364:1762-1767
A 25-year old woman presented for evaluation of abdominal pain. Her discomfort had begun 6 months earlier and was localized to the right upper quadrant. She described a constant pressure unrelated to food intake and associated with intermittent nausea and vomiting.
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Interactive Medical Case
A Sweet Source of Abdominal Pain
A 25-year old woman presented to her primary care physician for evaluation of abdominal pain. Her abdominal discomfort began six months earlier, and was localized to the right upper quadrant. She described a constant pressure unrelated to food intake and associated with intermittent nausea and…
- April 14, 2011
- Ross J.J., Rogal S.S., Ukomadu C.
- N Engl J Med 2011; 364:e30
- Free Full Text
- CME
A 25-year old woman presented to her primary care physician for evaluation of abdominal pain. Her abdominal discomfort began six months earlier, and was localized to the right upper quadrant. She described a constant pressure unrelated to food intake and ...
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Original Article
Carbamazepine-Induced Toxic Effects and HLA-B*1502 Screening in Taiwan
The Stevens–Johnson syndrome (SJS) and its related disease, toxic epidermal necrolysis (TEN), are two of the most serious adverse reactions caused by drugs. SJS is characterized by high fever, malaise, and a rapidly developing, blistering exanthema of macular papules and target-like lesions,…
- March 24, 2011
- Chen P., Lin J.-J., Lu C.-S., et al.
- N Engl J Med 2011; 364:1126-1133
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In this prospective study, Han Chinese subjects who were candidates for carbamazepine therapy were screened for the HLA-B*1502 allele because of its association with the Stevens–Johnson syndrome and toxic epidermal necrolysis.
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Original Article
HLA-A*3101 and Carbamazepine-Induced Hypersensitivity Reactions in Europeans
Carbamazepine is one of the most commonly prescribed drugs for the treatment of epilepsy, as well as trigeminal neuralgia and bipolar disorder. A minority of treated persons have hypersensitivity reactions that vary in prevalence and severity, with some forms associated with substantial morbidity…
- March 24, 2011
- McCormack M., Alfirevic A., Bourgeois S., et al.
- N Engl J Med 2011; 364:1134-1143
- Free Full Text
A strong association between the HLA-B*1502 allele and SJS and TEN induced by carbamazepine has been shown. This study involving Europeans implicates a different HLA allele, HLA-A*3101, in conferring susceptibility to a broad range of carbamazepine-induced reactions.
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Case Records of the Massachusetts General Hospital
Case 8-2011 — A 32-Year-Old Woman with Seizures and Cognitive Decline
Presentation of Case. A 32-year-old woman was seen in the neurogenetics clinic at this hospital because of seizures and cognitive decline. Absence seizures (staring spells) had reportedly begun when the patient was approximately 5 years of age, and atonic seizures (sudden loss of muscle tone…
- March 17, 2011
- Sims K.B., Cole A.J., Sherman J.C., Caruso P.A., Snuderl M.
- N Engl J Med 2011; 364:1062-1074
A 32-year-old woman had seizures since childhood, myoclonus, and recent cognitive decline. Family members had an autosomal-dominant pattern of neurologic disease. Diagnostic testing was performed. Cognitive decline continued; the patient died 2 years later. An autopsy was performed.
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Original Article
Long-Term Mortality in Childhood-Onset Epilepsy
Few studies have evaluated long-term mortality in well-characterized cohorts of children with epilepsy. With a few notable exceptions,– studies involving adults are usually retrospective.– In pediatric series, the follow-up is generally 5 to 10 years.– In all series, autopsy confirmation of…
- December 23, 2010
- Sillanpää M. and Shinnar S.
- N Engl J Med 2010; 363:2522-2529
- Free Full Text
In this cohort study involving 245 Finnish children with epilepsy, after 40 years of follow-up, 60 subjects had died (24%), a rate three times as high as the expected age- and sex-adjusted mortality in the general population. A total of 33 of 60 deaths (55%) were related to epilepsy.
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Original Article
Everolimus for Subependymal Giant-Cell Astrocytomas in Tuberous Sclerosis
The tuberous sclerosis complex, an autosomal dominant disorder with a prevalence approaching 1 in 6000 live births, is a potentially devastating disorder characterized by benign tumors (hamartomas) in multiple organ systems, including the brain, skin, kidney, lung, heart, and retina. Mutations in…
- November 4, 2010
- Krueger D.A., Care M.M., Holland K., et al.
- N Engl J Med 2010; 363:1801-1811
- Free Full Text
Neurosurgical resection is standard for subependymal giant-cell astrocytomas (SEGAs) in tuberous sclerosis. Treatment with everolimus, which inhibits the mammalian target of rapamycin, a protein regulated by gene products involved in tuberous sclerosis, resulted in reduced SEGA volume and seizures.
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Images in Clinical Medicine
Agitation Associated with Acute Bladder Obstruction
Figure 1.
- October 21, 2010
- De Luca G.C. and Wijdicks E.F.M.
- N Engl J Med 2010; 363:1656
- Free Full Text
A 61-year-old man with mild cognitive impairment and a seizure disorder from traumatic brain injury sustained 3 years earlier presented to the emergency department while having a cluster of complex partial seizures. He had been receiving levetiracetam ...
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Original Article
Brief Report: Timing of De Novo Mutagenesis — A Twin Study of Sodium-Channel Mutations
De novo mutations cause sporadic forms of a range of mendelian disorders, including tuberous sclerosis, neurofibromatosis, achondroplasia, and Dravet's syndrome. Recently, de novo copy-number variations have been identified as a cause of sporadic cases of some mendelian disorders and perhaps more…
- September 30, 2010
- Vadlamudi L., Dibbens L.M., Lawrence K.M., et al.
- N Engl J Med 2010; 363:1335-1340
- Free Full Text
This study of monozygous twins, in which one twin has Dravet's syndrome and the other does not, suggests that the mutation occurred in the early morula that gave rise to the affected twin.
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Original Article
Suicide-Related Events in Patients Treated with Antiepileptic Drugs
Suicide is the 13th leading cause of death worldwide, and attempted suicide is a major cause of injury. Psychiatric disorders (especially affective conditions) increase the risk of suicide.– Epilepsy increases both the risk of suicide among patients with psychiatric disorders and the risk of the…
- August 5, 2010
- Arana A., Wentworth C.E., Ayuso-Mateos J.L., Arellano F.M.
- N Engl J Med 2010; 363:542-551
- Free Full Text
In this large observational study based on data collected as part of clinical care in the United Kingdom, antiepileptic-drug treatment was not associated with an increased risk of suicide-related events among patients with epilepsy, but the use of these drugs was associated with suicide-related events in patients with depression.
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Case Records of the Massachusetts General Hospital
Case 22-2010 — An 87-Year-Old Woman with Dementia and a Seizure
Presentation of Case. An 87-year-old woman with a history of dementia was admitted to this hospital because of a seizure. The patient had been in her usual state of health until 2 days before admission, when she appeared to be fatigued, sleeping later each morning than usual. One hour before…
- July 22, 2010
- Greenberg S.M., Rapalino O., Frosch M.P.
- N Engl J Med 2010; 363:373-381
An 87-year-old woman with a history of dementia was admitted to this hospital because of a seizure. A diagnosis of possible Alzheimer's disease had been made 4 years earlier; at baseline, she recognized only her husband and children. On examination, she was unresponsive. Magnetic resonance imaging scans of the brain revealed T₂-weighted hyperintensities in the white matter involving both cerebral hemispheres, as well as innumerable small foci of susceptibility-weighted artifact at the cortical–subcortical junction. Despite a temporary improvement after treatment, she died of pneumonia a few days later. An autopsy was performed.
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Original Article
Valproic Acid Monotherapy in Pregnancy and Major Congenital Malformations
Valproic acid, which has been used for the treatment of seizure for more than 30 years, has long been recognized as a teratogen. Maternal exposure to valproic acid monotherapy during the first trimester was first linked to an increased risk of congenital spina bifida in the 1980s–; subsequent…
- June 10, 2010
- Jentink J., Loane M.A., Dolk H., et al.
- N Engl J Med 2010; 362:2185-2193
- Free Full Text
This large case–control study used a European database to assess associations between first-trimester valproic acid monotherapy and 14 malformations reported previously to be linked to valproic acid use in early pregnancy. Valproic acid monotherapy was associated with significantly increased risks for 6 of the 14 malformations, including spina bifida, atrial septal defect, cleft palate, hypospadias, polydactyly, and craniosynostosis, as compared with no antiepileptic-drug use or use of other antiepileptic drugs.
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Medical Meetings Pediatrics Conferences and Meetings

2012 Certifying Examinations of the American Board of Pediatrics

The general pediatrics examination will be held in various cities, Oct. 16-18. Registration for first-time applicants is ongoing through May 3. Registration for re-registrants is ongoing through May 24. The following subspecialty examinations will be held in various cities: "Hospice and Palliative Medicine" (Oct. 4); "Pediatric Transplant Hepatology" (Oct. 11); "Pediatric Cardiology" (Nov. 7); "Pediatric Pulmonology" (Nov. 8); "Medical Toxicology" (Nov. 12); and "Pediatric Critical Care Medicine" (Nov. 14). Registration for first-time applicants is ongoing through April 30. Registration for re-registrants is ongoing through June 15.

Contact the American Board of Pediatrics, 111 Silver Cedar Court, Chapel Hill, NC 27514-1513; or call (919) 929-0461; or fax (919) 918-7114 or (919) 929-9255; or see http://www.abp.org .

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