The rationale was to develop recommendations on the use of 18 F-FDG PET in breast, colorectal, esophageal, head and neck, lung, pancreatic, and thyroid cancer; lymphoma, melanoma, and sarcoma; and unknown primary tumor. Outcomes of interest included the use of 18 F-FDG PET for diagnosing, staging, and detecting the recurrence or progression of cancer. Methods: A search was performed to identify all published randomized controlled trials and systematic reviews in the literature. An additional search was performed to identify relevant unpublished systematic reviews. These publications comprised both retrospective and prospective studies of varied methodologic quality. The anticipated consequences of false-positive and false-negative tests when evaluating clinical usefulness, and the impact of 18 F-FDG PET on the management of cancer patients, were also reviewed. Results and Conclusion: 18 F-FDG PET should be used as an imaging tool additional to conventional radiologic methods such as CT or MRI; any positive finding that could lead to a clinically significant change in patient management should be confirmed by subsequent histopathologic examination because of the risk of false-positive results. 18 F-FDG PET should be used in the appropriate clinical setting for the diagnosis of head and neck, lung, or pancreatic cancer and for unknown primary tumor. PET is also indicated for staging of breast, colon, esophageal, head and neck, and lung cancer and of lymphoma and melanoma. In addition, 18 F-FDG PET should be used to detect recurrence of breast, colorectal, head and neck, or thyroid cancer and of lymphoma. PET is an imaging technique that provides unique information about the molecular and metabolic changes associated with disease. The technology has existed for more than 30 years but has been used clinically for only the last 10-15 years. In this period, dramatic improvements in technology, the routine availability of medical cyclotrons (to produce the necessary short-lived positron emitters), and favorable reimbursement decisions in the late 1990s have led to a tremendous increase in the use of this technology. The major area of clinical application is currently in oncology, with some application in cardiology and neurology.PET requires the use of molecules (radiopharmaceuticals) that are labeled with radioactive nuclides. The amounts of radiolabeled material administered are extremely small (10 26 -10 29 g) and have essentially no pharmacologic effect. In this regard, PET has the unique ability to assess molecular alterations associated with disease without perturbing or altering the fundamental underlying molecular and biochemical processes. Although the number of molecular probes that can be radiolabeled with positron emitters is extremely large, and clinical investigational uses number in the thousands, clinical practice has been limited principally to the use of a glucose analog labeled with the positron emitter 18 F-FDG. 18 F-FDG was first synthesized in 1978 (1) and has become the most commonly used radioph...

Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). However, we identified a 7 Mb interval containing a susceptibility locus (ANE1) in a family segregating recurrent ANE as an incompletely penetrant, autosomal-dominant trait. We now report that all affected individuals and obligate carriers in this family are heterozygous for a missense mutation (c.1880C-->T, p.Thr585Met) in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2). To determine whether this mutation is the susceptibility allele, we screened controls and other patients with ANE who are unrelated to the index family. Patients from 9 of 15 additional kindreds with familial or recurrent ANE had the identical mutation. It arose de novo in two families and independently in several other families. Two other patients with familial ANE had different RANBP2 missense mutations that altered conserved residues. None of the three RANBP2 missense mutations were found in 19 patients with isolated ANE or in unaffected controls. We conclude that missense mutations in RANBP2 are susceptibility alleles for familial and recurrent cases of ANE.

MOG-ON and AQP4-ON are more commonly bilateral and longitudinally extensive. MOG-ON tends to involve the anterior optic pathway, whereas AQP4-ON the posterior optic pathway.

To investigate whether or not the disparity in disease progression in those with pediatric-onset compared with adult-onset multiple sclerosis (MS) is due to differences in relapse rates. Design: Inception cohort. Mean follow-up times were 3.67 (standard deviation, 1.64) and 3.98 (standard deviation, 1.17) years in the pediatric and adult groups, respectively. Setting: Comprehensive MS centers. Patients: Patients with relapsing-remitting MS who were seen at the pediatric and adult MS centers at Massachusetts General and Brigham and Women's Hospitals, respectively, 12 months or less from onset of first symptom in July 2001 or later and were followed up for 12 months or longer. One hundred ten patients with adult-onset and 21 patients with pediatric-onset MS were included. Three eligible patients with adult-onset MS were excluded owing to incomplete records. Main Outcome Measure: Annualized relapse rates were compared between pediatric-onset and adult-onset patients using the proportional means model. Results: The annualized relapse rate in the pediatriconset group was significantly higher than that in the adultonset group (1.13 vs 0.40; PϽ.001) with an adjusted rate ratio of 2.81 (95% confidence interval, 2.07-3.81). When we controlled for time spent undergoing diseasemodifying treatment in the analysis, the difference between the groups remained highly significant (adjusted rate ratio, 2.82; 95% confidence interval, 2.08-3.83; PϽ.001). When age at disease onset was treated as a continuous variable, a highly significant association between age and relapse rate was observed (PϽ.001). Conclusions: Relapses are more frequent in patients with pediatric-onset compared with adult-onset MS in the disease-modifying treatment era. This finding suggests that patients with pediatric-onset MS experience a more inflammatory disease course than patients with adult onset of the disease.