MS incidence and prevalence in Africa, Asia, Australia and New Zealand: A systematic review.

OBJECTIVES: Studies of multiple sclerosis (MS) incidence and prevalence from Africa, Asia, Australia and New Zealand are relatively scarce. We systematically reviewed MS incidence and prevalence in these regions including a standardized evaluation of study quality. METHODS: We searched MEDLINE and EMBASE databases for studies of MS prevalence or incidence in Africa, Asia, Australia and New Zealand published in English or French between January 1, 1985 and January 31, 2011. Study quality was assessed using a standardized tool. All steps of the review were performed in duplicate. RESULTS: Of 3925 citations identified, 28 studies met inclusion criteria and 21 of these were from Asia. Quality scores ranged from 1/8 to 8/8; the lowest scores were observed in studies from Asia (median 4/8, IQR 3,6). Prevalence was lowest in South African Blacks (0.22/100,000) and highest amongst Australian-born individuals in Australia (125/100,000). Prevalence increased over time in many countries. MS prevalence increased with increasing latitude only in some regions, and prevalence varied significantly with ethnicity. Eight studies reported incidence, which ranged from 0.67/100,000/year in Taiwan to 3.67/100,00/year in Australia. CONCLUSIONS: This comprehensive study provides an update of MS epidemiology in Africa, Asia, Australia, and New Zealand. Incidence and prevalence were lowest in Africa and Asia and highest in Australia, but many Asian studies were of poor quality. Use of consistent case ascertainment methods, standardized data collection tools, and similar outcomes would all improve study quality and comparability. The underlying basis of observed ethnic differences is an important area for future study.

Cyclophosphamide therapy in pediatric multiple sclerosis.

OBJECTIVE: To review our multicenter experience with cyclophosphamide in the treatment of children with multiple sclerosis (MS). METHODS: Retrospective chart review of children with MS treated with cyclophosphamide. Demographic, clinical, treatment, and MRI parameters were collected. RESULTS: We identified 17 children with MS treated with cyclophosphamide. All but one had worsening of Expanded Disability Status Scale scores or multiple relapses prior to treatment initiation. Children were treated with one of three regimens: 1) induction therapy alone; 2) induction therapy with pulse maintenance therapy; or 3) pulse maintenance therapy alone. Treatment resulted in a reduction in relapse rate and stabilization of disability scores assessed 1 year after treatment initiation in the majority of patients. Longer follow-up was available for most cases. Cyclophosphamide was well tolerated in most patients. However, side effects included vomiting, transient alopecia, osteoporosis, and amenorrhea. One patient developed bladder carcinoma that was successfully treated. CONCLUSIONS: Cyclophosphamide is an option for the treatment of children with aggressive multiple sclerosis refractory to first-line therapies. Recommendations regarding patient selection, treatment administration, and monitoring are discussed.

Prospective comparison of clinical and computed tomography assessment in detecting uterine perforation with intracavitary brachytherapy for carcinoma of the cervix.

Brachytherapy (BT) is an essential component of radical treatment for cervix cancer. Uterine perforation is a potential complication of intrauterine applicator (tandem) insertion. Postprocedure pelvic computed tomography (CT) scans are routinely performed at this center. The objective of this study was to prospectively compare radiation oncologists' (RO) clinical impression of satisfactory tandem placement with actual tandem placement as determined from pelvic CT. Patients with cervix cancer undergoing low-dose rate BT from April 2003 to December 2005 were prospectively identified. After tandem placement, patients were brought to the radiotherapy department for pelvic imaging (plain films and CT). Prior to viewing imaging, the RO specified whether they were concerned vs not concerned about uterine perforation. The CT was then reviewed to determine actual tandem placement (perforation vs no perforation). One hundred twenty-four sequential tandem insertions were performed in 114 patients and eligible for analysis. The incidence of CT detected uterine perforation was 13.7% (17/124). Physician concern, age greater than or equal to 60, and tumor size were significant predictors of uterine perforation (P < 0.0001, P= 0.0019, and P= 0.0016, respectively). The overall sensitivity and specificity for physician concern was 52.9% and 84.1%, respectively. CT detected perforation in 8.2% (8/98) of insertions where the RO was clinically confident of correct tandem placement. Pelvic CT was a useful modality to accompany clinical assessment in identifying uterine perforation in cervix BT. As a low but potentially clinical significant number of perforations identified on CT were not suspected clinically, we recommend acquiring pelvic imaging in all patients following tandem insertion to ensure intrauterine tandem positioning.

Elevated mutant frequencies and increased C : G-->T : A transitions in Mlh1-/- versus Pms2-/- murine small intestinal epithelial cells.

Mutations in DNA mismatch repair (MMR) genes are associated with increased genomic instability and susceptibility to cancer. Mice rendered deficient in either Mlh1 or Pms2 as a result of gene targeting are prone to tumorigenesis, particularly, lymphomas. In addition, although Mlh1-/- mice also develop small intestinal adenomas and adenocarcinomas, Pms2-/- animals remain free of such tumors. To establish whether this phenotypic dichotomy might be associated with a quantitative and/or qualitative difference in genomic instability in these mice, we determined small intestinal epithelial cell DNA mutant frequency and mutation spectrum using a transgenic lambda-phage lacI reporter system. Mutant frequencies obtained from both Mlh1-/- and Pms2-/- mice revealed elevations of 18- and 13-fold, respectively, as compared to their wild-type littermates. Interestingly, we found that C : G-->T : A transitions were significantly elevated in Mlh1-/- mice, accounting in large measure for the 1.5-fold lacI mutant frequency increase seen in these animals. We hypothesize that the increased level of C : G-->T : A mutations may explain, in part, why Mlh1-/- mice, but not Pms2-/- mice, develop small intestinal tumors. Furthermore, the difference in the lacI mutational spectrum of Mlh1-/- and Pms2-/- mice suggests that other MutL-like heterodimers may play important roles in the repair of G : T mispairs arising within murine small intestinal epithelial cells.

Computed tomographic simulation of craniospinal fields in pediatric patients: improved treatment accuracy and patient comfort.

PURPOSE: To reduce the time required for planning and simulating craniospinal fields through the use of a computed tomography (CT) simulator and virtual simulation, and to improve the accuracy of field and shielding placement. METHODS AND MATERIALS: A CT simulation planning technique was developed. Localization of critical anatomic features such as the eyes, cribriform plate region, and caudal extent of the thecal sac are enhanced by this technique. Over a 2-month period, nine consecutive pediatric patients were simulated and planned for craniospinal irradiation. Four patients underwent both conventional simulation and CT simulation. Five were planned using CT simulation only. The accuracy of CT simulation was assessed by comparing digitally reconstructed radiographs (DRRs) to portal films for all patients and to conventional simulation films as well in the first four patients. RESULTS: Time spent by patients in the CT simulation suite was 20 min on average and 40 min maximally for those who were noncompliant. Image acquisition time was <10 min in all cases. In the absence of the patient, virtual simulation of all fields took 20 min. The DRRs were in agreement with portal and/or simulation films to within 5 mm in five of the eight cases. Discrepancies of > or =5 mm in the positioning of the inferior border of the cranial fields in the first three patients were due to a systematic error in CT scan acquisition and marker contouring which was corrected by modifying the technique after the fourth patient. In one patient, the facial shield had to be moved 0.75 cm inferiorly owing to an error in shield construction. CONCLUSIONS: Our analysis showed that CT simulation of craniospinal fields was accurate. It resulted in a significant reduction in the time the patient must be immobilized during the planning process. This technique can improve accuracy in field placement and shielding by using three-dimensional CT-aided localization of critical and target structures. Overall, it has improved staff efficiency and resource utilization.