Increased fracture rates in Turner's syndrome: a nationwide questionnaire survey

BACKGROUND AND OBJECTIVES: Reduced bone mineral content (BMC) and bone mineral density (BMD) have previously been reported in Turner's syndrome, although appropriate GH treatment and early induction of puberty seem to permit normal bone mass accumulation. Furthermore, an increased risk of fractures and osteoporosis have been reported in a registry study. The aim of the present study was to further characterize the risk of fractures in TS and to explore risk factors, in a historical follow-up survey based on a self-administered questionnaire. STUDY GROUPS: The questionnaire was issued to all females with TS (n = 632) in Denmark and to 1888 randomly selected controls (C) matched for age and geographical region. A total of 322 patients (51%) and 1169 controls (62%) returned the questionnaire. RESULTS: TS women were younger than C (30 years, range: 1-73 years vs. 34 years, range 2-82 years, P < 0.0005), smoked less often (17%vs. 27%, P < 0.0005), and had less frequent spontaneous menstruation (18%vs. 86%, P < 0.0005). In contrast, they used hormonal replacement therapy (HRT) more often (71%vs. 7%, P < 0.0005). The median age at start of HRT was 16 years (range 8-59 years) in TS vs. 42 years (range 12-53 years) in C (P < 0.0005). Above the age of 15 years, 83% of TS and 8% of C used HRT. GH had been used by 37% of TS but only 0.2% of C. Both type 1 and 2 diabetes were increased sevenfold among TS. Altogether, 77 individuals with TS had 109 fractures. The fracture risk was increased in TS [hazard ratio (HR, status) 1.35, confidence interval (CI) 1.04-1.75, P = 0.025]. Time to first fracture was reduced in TS (53 +/- 2 vs. 63 +/- 1; log-rank P = 0.03). Spontaneous menstruation was protective in females above 13 years of age (HR: 0.70, CI 0.54-0.93, P = 0.012). A history of parental fractures increased the risk (HR 1.92, CI 1.62-2.27, P < 0.001). Fractures of the forearm was more frequent among TS (P = 0.02). CONCLUSION: The present nationwide survey, based on questionnaires, confirms an increased risk of early fractures in TS, especially in those without ovarian function and with a positive family history of fracture and osteoporosis. It thereby emphasizes the need for being vigilant with respect to BMD measurements in these patients.     

Ischemic lesion water homeostasis after thrombectomy for large vessel occlusion stroke within the anterior circulation: The impact of age

The effect of age on lesion pathophysiology in the context of thrombectomy has been poorly investigated. We aimed to investigate the impact of age on ischemic lesion water homeostasis measured with net water uptake (NWU) within a multicenter cohort of patients receiving thrombectomy for anterior circulation large vessel occlusion (LVO) stroke. Lesion-NWU was quantified in multimodal CT on admission and 24 h for calculating Δ-NWU as their difference. The impact of age and procedural parameters on Δ-NWU was analyzed. Multivariable regression analysis was performed to identify significant predictors for Δ-NWU. Two hundred and four patients with anterior circulation stroke were included in the retrospective analysis. Comparison of younger and elderly patients showed no significant differences in NWU on admission but significantly higher Δ-NWU (p = 0.005) on follow-up CT in younger patients. In multivariable regression analysis, higher age was independently associated with lowered Δ-NWU (95% confidence interval: −0.59 to −0.16, p < 0.001). Although successful recanalization (TICI ≥ 2b) significantly reduced Δ-NWU progression by 6.4% (p < 0.001), younger age was still independently associated with higher Δ-NWU (p < 0.001). Younger age is significantly associated with increased brain edema formation after thrombectomy for LVO stroke. Younger patients might be particularly receptive targets for future adjuvant neuroprotective drugs that influence ischemic edema formation.     

Comparative analysis of dimethyl fumarate and fingolimod in relapsing–remitting multiple sclerosis

Journal of Neurology - Dimethyl fumarate and fingolimod are oral disease modifying treatments (DMTs) that reduce relapse activity and slow disability worsening in relapsing–remitting multiple...     

Anterior vs Posterior Hippocampal Subfields in an Extended Psychosis Phenotype of Multidimensional Schizotypy in a Nonclinical Sample

Numerous studies have implicated involvement of the hippocampus in the etiology and expression of schizophrenia-spectrum psychopathology, and reduced hippocampal volume is one of the most robust brain abnormalities reported in schizophrenia. Recent studies indicate that early stages of schizophrenia are specifically characterized by reductions in anterior hippocampal volume; however, studies have not examined hippocampal volume reductions in subclinical schizotypy. The present study was the first to examine the associations of positive, negative, and disorganized schizotypy dimensions with hippocampal subfield volumes in a large sample (n = 195) of nonclinically ascertained young adults, phenotyped using the Multidimensional Schizotypy Scale (MSS). Hippocampal subfields were analyzed from high-resolution 3 Tesla structural magnetic resonance imaging scans testing anatomical models, including anterior vs posterior regions and the cornu ammonis (CA), dentate gyrus (DG), and subiculum subfields separately for the left and right hemispheres. We demonstrate differential spatial effects across anterior vs posterior hippocampus segments across different dimensions of the schizotypy risk phenotype. The interaction of negative and disorganized schizotypy robustly predicted left hemisphere volumetric reductions for the anterior and total hippocampus, and anterior CA and DG, and the largest reductions were seen in participants high in negative and disorganized schizotypy. These findings extend previous early psychosis studies and together with behavioral studies of hippocampal-related memory impairments provide the basis for a dimensional neurobiological hippocampal model of schizophrenia risk. Subtle hippocampal subfield volume reductions may be prevalent prior to the onset of detectable prodromal clinical symptoms of psychosis and play a role in the etiology and development of such conditions.     

Small and large fiber sensory polyneuropathy in type 2 diabetes: Influence of diagnostic criteria on neuropathy subtypes

Diabetic polyneuropathy (DPN) can be classified based on fiber diameter into three subtypes: small fiber neuropathy (SFN), large fiber neuropathy (LFN), and mixed fiber neuropathy (MFN). We examined the effect of different diagnostic models on the frequency of polyneuropathy subtypes in type 2 diabetes patients with DPN. This study was based on patients from the Danish Center for Strategic Research in Type 2 Diabetes cohort. We defined DPN as probable or definite DPN according to the Toronto Consensus Criteria. DPN was then subtyped according to four distinct diagnostic models. A total of 277 diabetes patients (214 with DPN and 63 with no DPN) were included in the study. We found a considerable variation in polyneuropathy subtypes by applying different diagnostic models independent of the degree of certainty of DPN diagnosis. For probable and definite DPN, the frequency of subtypes across diagnostic models varied from: 1.4% to 13.1% for SFN, 9.3% to 21.5% for LFN, 51.4% to 83.2% for MFN, and 0.5% to 14.5% for non‐classifiable neuropathy (NCN). For the definite DPN group, the frequency of subtypes varied from: 1.6% to 13.5% for SFN, 5.6% to 20.6% for LFN, 61.9% to 89.7% for MFN, and 0.0% to 6.3% for NCN. The frequency of polyneuropathy subtypes depends on the type and number of criteria applied in a diagnostic model. Future consensus criteria should clearly define sensory functions to be tested, methods of testing, and how findings should be interpreted for both clinical practice and research purpose.