The great mimicker: Phenotypic overlap between constitutional mismatch repair deficiency and Tuberous Sclerosis complex

Constitutional mismatch repair deficiency is a rare cancer predisposition syndrome caused by biallelic mutations in one of the four mismatch repair genes. Patients are predisposed to various tumors including hematological malignancies, brain tumors and colorectal carcinomas. Phenotypic overlap with Neurofibromatosis-1 is well known, with most patients presenting with café-au-lait macules. Other common features include axillary and/or inguinal freckling and intracranial MRI foci of high T2W/FLAIR signal intensity similar to the typical FASI seen in Neurofibromatosis-1. In this cohort of eight patients with constitutional mismatch repair deficiency we describe overlapping phenotypical features with Tuberous Sclerosis complex. In addition to “ash-leaf like” hypomelanotic macules (five patients), we detected intracranial tuber-like lesions (three patients), renal cysts (three patients) and renal angiomyolipomas (two patients). All our patients also had Neurofibromatosis-1 like features, mainly café-au-lait macules. This study suggests that features of Tuberous sclerosis especially when overlapping with those of Neurofibromatosis 1 or malignancies atypical for these syndromes should raise the possibility of constitutional mismatch repair deficiency. Correct diagnosis is essential for appropriate genetic counseling and pre-emptive cancer surveillance.     

The effect of increasing sets (within one treatment session) and different set durations (between treatment sessions) of lumbar spine posteroanterior mobilisations on pressure pain thresholds

Spinal mobilisations are a common form of treatment intervention applied by physiotherapists in clinical practice to manage musculoskeletal pain and/or dysfunction. Previous research has demonstrated that mobilisations cause a hypoalgesic effect. However, there is very little research investigating the optimal treatment dose inducing this effect.AimTo investigate the effect of the number of sets (up to 5) and different durations (30 vs. 60 s) on pressure pain thresholds (PPTs) at different sites.MethodsThis single-blinded, randomised, same subject repeated measures crossover design included 19 asymptomatic healthy volunteers. The participants received 5 sets of either 30 or 60 s of postero-anterior mobilisations to L4 on different days. PPTs were measured immediately before, between and after the intervention at 4 different standardised sites.ResultsA 4-way ANOVA analysis revealed that there was no statistically significant difference between 30 versus 60 s of mobilisations. However, there was a tendency for PPT values to be higher for the 60 s intervention. All PPT measurements after the interventions were significantly higher than the baseline. Only the measurement after the 4th set of mobilisations was significantly higher than the measurement after the 1st set (p = 0.035).ConclusionsThe results suggest that in order to induce the greatest local hypoalgesia, at least 4 sets of mobilisations are required. The different durations of 30 versus 60 s of mobilisation may not change the extent of the hypoalgesic effect.     

Assessment of the coagulation profile in hemato-oncological patients receiving ATG-based conditioning treatment for allogeneic stem cell transplantation

Antithymocyte globulin (ATG) is increasingly used in pre-allogeneic stem cell transplantation (allo-SCT) conditioning regimens to prevent graft rejection and graft-versus-host disease. However, ATG was also found to be associated with increased incidence of thrombosis during organ transplantation. In the present study, we tested the coagulation status of 21 patients with hematologic malignancies undergoing allo-SCT who received ATG-based (11 patients) or non-ATG-based (10) conditioning treatment. We assessed several thrombophilia markers as well as circulating total and endothelial microparticles (TMP/EMP) and soluble CD40 ligand (CD40L). No significant difference in the mean values of prothrombin time, partial thromboplastin time, fibrinogen, antithrombin, protein C, protein S, thrombin-antithrombin III complex, homocysteine levels, prevalence of genetic thrombophilia markers and levels of EMP, TMP or CD40L was observed between the ATG-treated and ATG-untreated patients, as well as before and after conditioning in each group separately. Platelet counts decreased significantly in ATG-treated patients; however, this decrease was not associated with clinical or laboratory evidence of disseminated intravascular coagulation. No patient developed thromboembolic event or veno-occlusive liver disease. Our results suggest that allo-SCT is not associated with increased hypercoagulability and addition of ATG to conditioning regimen has no significant procoagulant effect.     

Changes in the EEG spectral power during dual-task walking with aging and Parkinson’s disease: initial findings using Event-Related Spectral Perturbation analysis

Journal of Neurology - The ability to maintain adequate motor-cognitive performance under increasing task demands depends on the regulation and coordination of neural resources. Studies have shown...     

The viability of the Parenting Representations Interview for assessing and measuring change in parents of adolescents

Parents’ representations include parents’ views of their adolescent, of their own parenting and of the parent–adolescent relationship. Two longitudinal studies of parents and their adolescent sons and daughters support the validity of scales coding mothers in the Parenting Representations Interview-Adolescence (PRI-A). The studies, conducted in Israel during the transition from home to military service, demonstrated that three dimensions derived from the PRI-A: positive representations of adolescents, negative emotionality and inadequate boundaries were associated with adolescents’ AAI variables, relatedness-autonomy behaviors with mothers, and with other indicators, such as adolescents’ wellbeing, romantic intimacy and individuation. Examining parenting representations could help practitioners pinpoint targets for intervention and evaluate the changes that families go through during psychotherapy, as well as the therapeutic process and its outcomes. The findings support the viability of the PRI for use in attachment based interventions for adolescents.     

Pituitary function in children following infectious diseases of the central nervous system

Recent studies in adults suggest that pituitary deficiencies develop in a considerable proportion of patients who recover from infectious meningitis. The aim of this study was to evaluate pituitary function of children with a history of meningitis. Seventy-nine children were admitted to the Safra Children’s Hospital due to meningitis between 2007 and 2010. Twenty-four families were lost for follow-up, 55 were interviewed by phone and 14 (9 males) participated in the study. Evaluation included medical history, physical examination, auxological measurements and basal levels of TSH, fT4, cortisol and IGF1. Children with abnormal results were followed for a year and dynamic testing was performed when indicated. Mean age at time of infectious meningitis was 3.8 ± 5.4 years (range 0.03–15.8), and at clinical evaluation 6.4 ± 6.4 (range 1.2–20). The interval between the acute event and evaluation was 2.7 ± 1.2 years. Thyroid function tests and basal cortisol levels were normal for all children. Three children had low IGF1 levels; however over a year of follow-up two of them had normal height and growth velocity, making growth hormone deficiency unlikely. One child had low height SDS, but exhibited a normal response to a growth hormone stimulation test. Pituitary dysfunction with overt clinical symptoms is not a frequent consequence of acute meningitis in children. Follow-up of growth and puberty of children post-meningitis by the primary care physician is probably sufficient. Invasive assessments should be reserved for selected cases where there is slow growth or other clinical suspicion of hypopituitarism.