The positive and the negative impacts of spasticity in patients with long-term neurological conditions: an observational study.

PURPOSE: To describe the positive and negative impacts of spasticity across different neurological disorders using the Patient Reported Impact of Spasticity Measure (PRISM), deduce any associations between severity of spasticity and its impact, and assess for differences across diagnostic subgroups. MATERIALS AND METHODS: PRISM, a spasticity-specific quality of life questionnaire validated in patients with spinal cord injuries, was given to 97 follow-up patients attending a spasticity clinic prior to symptom assessment using the REsistance to PAssive movement Scale (REPAS). RESULTS: Patients described a minor level of positive impact and a marked negative impact in the domains of "Psychological Agitation," "Daily Activities," "Need for Assistance/Positioning" and "Social Avoidance/Anxiety." Spasticity severity was, in general, a poor predictor of perceived impact, although severity and localisation of spasticity was modestly correlated with "Need for Assistance/Positioning" and "Social Embarrassment" levels. Despite comparable levels of spasticity severity, people with MS expressed a more substantial impact across some PRISM domains than did patients in other groups. CONCLUSION: PRISM can be useful to assess the impact of spasticity in various neurological conditions although further validation studies are needed.Implications for RehabilitationThe localisation of spasticity in both legs or the right arm can produce a significant impact on 'Need for Assistance/Positioning' and 'Social Embarrassment'.People with MS may experience a greater impact of spasticity than those with other neurological conditions, particularly in the domains of Social Avoidance/Anxiety and Psychological Agitation.Coexisting factors such as anxiety, depression, fatigue and pain should be investigated together with spasticity.PRISM can assist in goal setting and treatment of people with spasticity secondary to different neurological conditions.

Interventions to support Choosing Wisely for coagulation studies in the emergency department.

OBJECTIVE: To evaluate the effectiveness of two different strategies designed to facilitate implementation of Choosing Wisely Australia guidelines, aiming to reduce unnecessary coagulation study blood tests in patients presenting to a metropolitan hospital ED. METHOD: In this real-world quality improvement study, the first intervention tested was an education strategy. The second intervention was physically removing coagulation pathology tubes from the bedside trolleys in the ED. Data were collected about clinical appropriateness of testing, as per the Choosing Wisely Australia guideline and total volume of coagulation studies ordered. RESULTS: No reduction in inappropriate coagulation testing was observed following the education intervention whereas a significant reduction in inappropriate coagulation testing was seen after the second intervention (inappropriate testing reduced from 73.8% to 53.0%). CONCLUSION: Physically removing coagulation pathology tubes from the trolleys was found to be effective at reducing unnecessary testing.

Clinical features, molecular results, and management of 12 individuals with the rare arthrochalasia Ehlers-Danlos syndrome.

Arthrochalasia Ehlers-Danlos syndrome (aEDS) is a rare autosomal dominant connective tissue disorder that is characterized by congenital bilateral hip dislocations, severe generalized joint hypermobility, recurrent joint (sub)luxations, and skin hyperextensibility. To date, 42 patients with aEDS have been published. We report 12 patients with aEDS from 10 families with 6 unpublished individuals and follow-up data on 6 adult patients. The clinical features are largely comparable with patients reported in the literature. Most (n = 10) patients had variants leading to (partial) loss of exon 6 of the COL1A1 or COL1A2 genes. One patient did not have a previously reported likely pathogenic COL1A1 variant. Data regarding management were retrieved. Hip surgery was performed in 5/12 patients and 3/12 patients underwent spinal surgery. As much as 4/12 patients were wheelchair-bound or unable to walk unaided. Fractures were present in 9/12 individuals with 1 patient requiring bisphosphonate treatment. Echocardiograms were performed in 10 patients and 2 individuals showed an abnormality likely unrelated to aEDS. One patient gave birth to two affected children and went through preterm labor requiring medication but had no additional complications. Of the eight adults in our cohort, the majority entered a career. Our data point toward a genotype-phenotype relationship with individuals with aEDS due to pathogenic COL1A1 variants causing complete or partial loss of exon 6 being more severely affected regarding musculoskeletal features. There is a significant lack of knowledge with regard to management of aEDS, particularly in adulthood. As such, systematic follow-up and multidisciplinary treatment is essential.

Loss-of-Function Variants in TBC1D32 Underlie Syndromic Hypopituitarism.

CONTEXT: Congenital pituitary hormone deficiencies with syndromic phenotypes and/or familial occurrence suggest genetic hypopituitarism; however, in many such patients the underlying molecular basis of the disease remains unknown. OBJECTIVE: To describe patients with syndromic hypopituitarism due to biallelic loss-of-function variants in TBC1D32, a gene implicated in Sonic Hedgehog (Shh) signaling. SETTING: Referral center. PATIENTS: A Finnish family of 2 siblings with panhypopituitarism, absent anterior pituitary, and mild craniofacial dysmorphism, and a Pakistani family with a proband with growth hormone deficiency, anterior pituitary hypoplasia, and developmental delay. INTERVENTIONS: The patients were investigated by whole genome sequencing. Expression profiling of TBC1D32 in human fetal brain was performed through in situ hybridization. Stable and dynamic protein-protein interaction partners of TBC1D32 were investigated in HEK cells followed by mass spectrometry analyses. MAIN OUTCOME MEASURES: Genetic and phenotypic features of patients with biallelic loss-of-function mutations in TBC1D32. RESULTS: The Finnish patients harboured compound heterozygous loss-of-function variants (c.1165_1166dup p.(Gln390Phefs*32) and c.2151del p.(Lys717Asnfs*29)) in TBC1D32; the Pakistani proband carried a known pathogenic homozygous TBC1D32 splice-site variant c.1372 + 1G > A p.(Arg411_Gly458del), as did a fetus with a cleft lip and partial intestinal malrotation from a terminated pregnancy within the same pedigree. TBC1D32 was expressed in the developing hypothalamus, Rathke's pouch, and areas of the hindbrain. TBC1D32 interacted with proteins implicated in cilium assembly, Shh signaling, and brain development. CONCLUSIONS: Biallelic TBC1D32 variants underlie syndromic hypopituitarism, and the underlying mechanism may be via disrupted Shh signaling.