Reliability of Handheld Dynamometry to Measure Focal Muscle Weakness in Neurofibromatosis Types 1 and 2.

OBJECTIVE: To determine a suitable outcome measure for assessing muscle strength in neurofibromatosis (NF) type 1 and NF2 clinical trials, we evaluated the intraobserver reliability of handheld dynamometry (HHD) and developed consensus recommendations for its use in NF clinical trials. METHODS: Patients ≥5 years of age with weakness in at least 1 muscle group by manual muscle testing (MMT) were eligible. Maximal isometric muscle strength of a weak muscle group and the biceps of the dominant arm was measured by HHD. An average of 3 repetitions per session was used as an observation, and 3 sessions with rest period between each were performed on the same day by a single observer. Intrasession and intersession intraclass correlation coefficients (ICCs) and coefficients of variation (CVs) were calculated to assess reliability and measurement error. RESULTS: Twenty patients with NF1 and 13 with NF2 were enrolled; median age was 12 years (interquartile range [IQR] 9-17 years) and 29 years (IQR 22-38 years), respectively. By MMT, weak muscle strength ranged from 2-/5 to 4+/5. Biceps strength was 5/5 in all patients. Intersession ICCs for the weak muscles were 0.98 and 0.99 in the NF1 and NF2 cohorts, respectively, and for biceps were 0.97 and 0.97, respectively. The median CVs for average session strength were 5.4% (IQR 2.6%-7.3%) and 2.9% (IQR 2.0%-6.2%) for weak muscles and biceps, respectively. CONCLUSION: HHD performed by a trained examiner with a well-defined protocol is a reliable technique to measure muscle strength in NF1 and NF2. Recommendations for strength testing in NF1 and NF2 trials are provided.

Comparison of hybrid 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging and positron emission tomography/computed tomography for evaluation of peripheral nerve sheath tumors in patients with neurofibromatosis type 1.

Rapidly enlarging, painful plexiform neurofibromas (PN) in neurofibromatosis type 1 (NF1) patients are at higher risk for harboring a malignant peripheral nerve sheath tumor (MPNST). Fludeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has been used to support more invasive diagnostic and therapeutic interventions. However, PET/CT imparts an untoward radiation hazard to this population with tumor suppressor gene impairment. The use of FDG PET coupled with magnetic resonance imaging (MRI) rather than CT is a safer alternative but its relative diagnostic sensitivity requires verification. Ten patients (6 females, 4 males, mean age 27 years, range 8-54) with NF1 and progressive PN were accrued from our institutional NF Clinic. Indications for PET scanning included increasing pain and/or progressive disability associated with an enlarging PN on serial MRIs. Following a clinically indicated whole-body FDG PET/CT, a contemporaneous PET/MRI was obtained using residual FDG activity with an average time interval of 3-4 h FDG-avid lesions were assessed for both maximum standardized uptake value (SUVmax) from PET/CT and SUVmax from PET/MR and correlation was made between the two parameters. 26 FDG avid lesions were detected on both PET/CT and PET/MR with an accuracy of 100%. SUVmax values ranged from 1.4-10.8 for PET/CT and from 0.2-5.9 for PET/MRI. SUVmax values from both modalities demonstrated positive correlation (r = 0.45, P < 0.001). PET/MRI radiation dose was significantly lower (53.35% ± 14.37% [P = 0.006]). In conclusion, PET/MRI is a feasible alternative to PET/CT in patients with NF1 when screening for the potential occurrence of MPNST. Reduction in radiation exposure approaches 50% compared to PET/CT.

Effect of lapatinib on meningioma growth in adults with neurofibromatosis type 2.

INTRODUCTION: Epidermal growth factor receptors EGFR and ErbB2 are overexpressed in schwannomas and meningiomas. Preclinical and clinical data indicate that lapatinib, an EGFR/ErbB2 inhibitor, has antitumor activity against vestibular schwannomas in neurofibromatosis type 2 (NF2) patients. Its antitumor activity against meningiomas, however, is unknown. METHODS: We conducted a retrospective review of patients with NF2 and progressive vestibular schwannomas treated on a phase 2 clinical trial with lapatinib (NCT00973739). We included patients with at least one volumetrically measurable meningioma (> 0.5 cm3) who received at least five 28-day courses of treatment. Patients received lapatinib 1500 mg daily. Meningioma response was assessed using 3-dimensional MRI volumetrics. Progressive meningioma growth and response were defined as + 20 and - 20% change in tumor volume from baseline, respectively. Off-treatment was defined as any period > 5 months without lapatinib. RESULTS: Eight patients (ages: 20-58 years) who met criteria had 17 evaluable meningiomas with a combined volume of 61.35 cc at baseline, 61.17 cc during treatment, and 108.86 cc (+ 77.44% change) off-treatment, p = 0.0033. Median time on-treatment and off-treatment was 15.5 and 16.7 months, respectively. On-treatment mean and median annualized growth rates were 10.67 and 1.32%, respectively. Off-treatment mean and median annualized growth rates were 20.05 and 10.42%, respectively. The best volumetric response was - 26.1% after 23 months on lapatinib. Two tumors increased > 20% volumetrically on-treatment, compared to eight tumors off-treatment. CONCLUSIONS: These data suggest that lapatinib may have growth-inhibitory effects on meningiomas in NF2 patients, and support prospective studies of lapatinib for NF2 patients with progressive meningiomas.

Policonsumo simultáneo de drogas en estudiantes de facultades de ciencias de la salud/ciencias médicas en siete universidades de cinco países de América Latina y un país del Caribe: implicaciones de género, legales y sociales / Simultaneous polydrug consuption among undergraduate students of health sciences of seven universities in five Latin American countries and one Caribean country: gender, legal and social implicacions / Policonsumo simultâneo de drogas entre estudantes de graduação de ciências da saúde de sete universidades em cinco países da América Latina e um país do Caribe: implicações de gênero, legal e sociais

El objetivo de este estudio fue comprender los patrones de policonsumo simultáneo de sustancias psicoactivas y sus implicaciones de género, legales y sociales, en estudiantes de primer y segundo año de las facultades de ciencias de la salud/ciencias médicas, en siete universidades de cinco países latinoamericanos, Colombia, Nicaragua, Chile, Brasil y El Salvador, y un país caribeño, Jamaica. El diseño fue un corte transversal. Las combinaciones de alcohol + tabaco y de alcohol + marihuana fueron las mas reportadas en todas las universidades, a excepción de alcohol + tabaco en Jamaica. Los factores asociados al policonsumo más referidos fueron "tener relaciones sexuales inesperada" en la universidad de Brasil, "tener relaciones sexuales sin protección" en las universidades de Chile, Colombia y Nicaragua, "tener problemas con su pareja sentimental" en la universidad de Jamaica, y "ausentarse de clases" en la universidad de El Salvador. Tres entornos se relacionaron, de manera positiva o negativa, con el policonsumo simultáneo de sustancias psicoactivas: estudiantil, familiar y de comportamiento sexual.

The objective of this study was to understand patterns of simultaneous polydrug use of psychoactive substances and its gender, legal and social implications, among first and second year undergraduate students in health sciences/medical sciences faculties from six universities in five Latin American countries, Colombia, Nicaragua, Chile, Brazil, and El Salvador, and one Caribbean country, Jamaica. The study design was cross-sectional. The combinations of alcohol + tobacco and alchol + cannabis were the most frequently reported in all universities, with the exception of alcohol + tabaco in Jamaica. The factors associated to polidrug use most frequently mentioned were "to have unexpected sexual relationships" in the Brazilian university, "to have unprotected sex" in the universities of Chile, Colombia and Nicaragua, "to have problems with his o her sentimental partner" in the Jamaican university, and "to skip classes" in the university of El Salvador. Three environments were related, positively or negatively, with simultaneous polydrug use of psychoactive substances: academic, familiar and sexual behavioral.

Estudo de corte transversal que teve por objetivo compreender os padrões de policonsumo simultâneo de substâncias psicoativas e suas implicações de gênero, direitos legais e sociais entre estudantes do primeiro e segundo ano de faculdades de ciencias da saúde/médicas, de sete universidades, em cinco países latinoamericanos e um do Caribe. Os resultados indicam que o uso de múltiplas drogas simultâneas como álcool + tabaco foi maior para as universidades na Colômbia, Nicarágua, Chile, Brasil e El Salvador, com exceção da Jamaica, seguido por policonsumo simultâneo de álcool + maconha. A consequencia mais comum entre os estudantes que usam mais de uma substância psicoativa é o "sexo eventual" na Universidade do Brasil; "ter relações sexuais sem proteção" nas Universidades do Chile, Colômbia e Nicarágua; "ter problemas com seu parceiro sentimental" na Universidade da Jamaica, e ausentar-se das aulas" para a Universidade de El Salvador. Conclui-se que os modelos representam a existência de três ambientes relacionados entre si, positiva ou negativamente, com o uso simultâneo de substâncias psicoativas: ou seja, estudante, família do aluno e comportamento sexual.

Exploration of simultaneous polydrug use: risk and protective factors in undergraduate students in one university, Kingston - Jamaica / Exploración del uso simultáneo de polisustancias y factores protectores y de riesgos en alumnos de pregrado en una universidad, Kingston - Jamica / Exploração do policonsumo simultâneo de drogas e fatores protetores e de riscos em estudantes de graduação de uma universidade, Kingston - Jamaica

Simultaneous polydrug use in undergraduate students was studied in one university in Kingston, Jamaica. The study was a cross-sectional, and used a survey method of data collection. We examined protective and risk factors associated with simultaneous polydrug use in a sample of 295 undergraduate students from the health and medical science departments in the university. Our results suggest that continued residence with family, family support, and students' emotional well-being are protective factors. On the other hand, ease of access of substance and limited emotional support may be considered risk factors. Our findings may inform preventive programs, though further research is required.

El policonsumo simultáneo de sustancias psicoactivas en estudiantes de una universidad fue estudiado en Kingston, Jamaica. El estudio fue de diseño transversal, y utilizó la modalidad de encueta para la recolección de datos. Examinamos factores de riesgo y de protección asociados al policonsumo simultáneo en una muestra de 295 estudiantes de pregrado de los departamentos de la salud y de la ciencia médica de la universidad participante. Nuestros resultados sugieren que la estancia continuada con la familia, el apoyo familiar, y el bienestar de los estudiantes son factores de riesgo. Por el contrario, la facilidad del acceso de las drogas y el apoyo emocional se podrían considerar como factores protectores. Estos hallazgos pueden informar programas preventivos, aunque se requiere investigación adicional.

O policonsumo simultâneo de drogas em estudantes de graduação de uma universidade foi estudado em Kingston, Jamaica. É um estudo de corte transversal utilizando o método survey para coleta de dados. Foram examinados os fatores de risco e de protecção associados com o policonsumo simultâneo, em uma amostra de 295 estudantes de graduação da are da saúde e do departamento ciências médicas da universidade participante no estudo. Os resultados deste estudo indicam que residir com a família, fornece uma sustentação maior e bem estar emocional, atuando como fatores protetores. Por outro lado, a facilidade de acesso as drogas e a sustentação emocional limitada atuaram como fatores de risco. Estes resultados podem informar os programas de prevenção, embora mais pesquisas sejam necessárias.