[Physiotherapeutic Care of Adults with Neuromuscular Diseases - an Online Survey of Physiotherapists in the City Area of Munich]. / Physiotherapeutische Versorgung von Erwachsenen mit Neuromuskulären Erkrankungen ­ Online-Befragung von Physiotherapeut*innen im Stadtgebiet München.

BACKGROUND AND AIM: Physiotherapy has a key role in the symptomatic treatment of neuromuscular disorders (NMD). In the health care of adults with NMD, there may be intransparency of physiotherapy processes due, among other factors, to disciplinary interfaces. This study describes the current state of physiotherapeutic care for adults with NMD and examines the needs of physiotherapists in improving the quality of physiotherapeutic care. METHODS: An online survey of physiotherapists in the city area of Munich was carried out using Lime Survey. The survey link was distributed in both inpatient and outpatient settings and with use of the snowball principle. The data on the closed and open questions were accordingly evaluated quantitatively descriptively and content-analytically. RESULTS: A total of 137 physiotherapists participated in the online survey, and information from 124 survey participants was included in the analyses. 62.4% (n=58) of them were involved in the treatment of adults with NMD. The most common physiotherapy prescription was "Physiotherapy for the treatment of central movement disorders" (KG-ZNS) (82.9%; n=34). Home visits and assistive devices were ranked as the most effective interventions. 69.1% (n=56) of survey participants would like more information on NMD, primarily in the form of e-learning (24.0%; n=37) and professional articles (21.4%; n=33). In addition to the identified need for information, there were requests for more in-depth interprofessional communication and increased time resources in physiotherapeutic treatment. CONCLUSION: The wide range of physiotherapeutic measures applied pursues, among other things, the goal of helping patients maintain their independence and is considered to be of great benefit in the care of adult patients with NMD. It is important to address the identified desire and need for information expressed by physiotherapists on the subject of NMD in the preferred form by means of low-threshold offers. The interprofessional communication should be intensified and time-related aspects should be considered in the issuing of prescriptions as well as with regard to a possible blank prescription option in the future, in order to achieve positive effects in the physiotherapeutic care of adult patients with NMD.

Functional validation of ABHD12 mutations in the neurodegenerative disease PHARC.

ABHD12 mutations have been linked to neurodegenerative PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and early-onset cataract), a rare, progressive, autosomal, recessive disease. Although ABHD12 is suspected to play a role in the lysophosphatidylserine and/or endocannabinoid pathways, its precise functional role(s) leading to PHARC disease had not previously been characterized. Cell and zebrafish models were designed to demonstrate the causal link between an identified new missense mutation p.T253R, characterized in ABHD12 from a young patient, the previously characterized p.T202I and p.R352* mutations, and the associated PHARC. Measuring ABHD12 monoacylglycerol lipase activity in transfected HEK293 cells demonstrated inhibition with mutated isoforms. Both the expression pattern of zebrafish abhd12 and the phenotype of specific antisense morpholino oligonucleotide gene knockdown morphants were consistent with human PHARC hallmarks. High abhd12 transcript levels were found in the optic tectum and tract, colocalized with myelin basic protein, and in the spinal cord. Morphants have myelination defects and concomitant functional deficits, characterized by progressive ataxia and motor skill impairment. A disruption of retina architecture and retinotectal projections was observed, together with an inhibition of lens clarification and a low number of mechanosensory hair cells in the inner ear and lateral line system. The severe phenotypes in abhd12 knockdown morphants were rescued by introducing wild-type human ABHD12 mRNA, but not by mutation-harboring mRNAs. Zebrafish may provide a suitable vertebrate model for ABHD12 insufficiency and the study of functional impairment and potential therapeutic rescue of this rare, neurodegenerative disease.

Full-field electroretinography and marked variability in clinical phenotype of Alström syndrome.

OBJECTIVES: To characterize the clinical phenotype and to study the course of disease in patients with Alström syndrome, with an emphasis on retinal function assessed with full-field electroretinography (ERG). METHODS: Three age- and sex-matched patients with Alström syndrome were selected from our retinitis pigmentosa register for repeated ophthalmologic examinations that included tests for color vision and visual fields using Goldmann perimetry and for repeated assessment of full-field ERGs. RESULTS: Electroretinography demonstrated cone-rod degeneration in all 3 patients. A concomitant impairment of color vision and visual fields was also observed as well as marked variation in retinal function and in disease severity. CONCLUSIONS: Full-field ERGs confirmed that Alström syndrome is associated with a cone-rod type of retinal degeneration. In this study, we have shown a striking variability in retinal function and disease onset and severity, which has, to our knowledge, not been described previously in Alström syndrome.

Phenotypes in defined genotypes including siblings with Usher syndrome.

OBJECTIVE: To characterize visual function in defined genotypes including siblings with Usher syndrome. METHODS: Thirteen patients with phenotypically different subtypes of Usher syndrome, including 3 families with affected siblings, were selected. Genetic analysis and ophthalmological examinations including visual fields, full-field electroretinography (ERG), multifocal electroretinography (mf ERG), and optical coherence tomography (OCT) were assessed. The patients' degree of visual handicap was evaluated by a questionnaire (ADL). RESULTS: Twelve of thirteen patients were genotyped as Usher 1B, 1D, 1F, 2A, 2C or 3A. In 12 of 13 patients examined with ERG the 30 Hz flickering light response revealed remaining cone function. In 3 of the patients with Usher type 1 mf ERG demonstrated a specific pattern, with a sharp distinction between the area with reduced function and the central area with remaining macular function and normal peak time. OCT demonstrated loss of foveal depression with distortion of the foveal architecture in the macula in all patients. The foveal thickness ranged from 159 to 384 µm and was not correlated to retinal function. Three siblings shared the same mutation for Usher 2C but in contrast to previous reports regarding this genotype, 1 of them diverged in phenotype with substantially normal visual fields, almost normal OCT and mf ERG findings, and only moderately reduced rod and cone function according to ERG. CONCLUSIONS: Evaluation of visual function comprising both the severity of the rod cone degeneration and the function in the macular region confirm phenotypical heterogeneity within siblings and between different genotypes of Usher syndrome.

Alteration of rod and cone function in children with Usher syndrome.

PURPOSE: To evaluate the retinal function, with emphasis on phenotype and rate of progression, in infants and children with different genotypes of Usher syndrome. METHODS: Fourteen children (2-10 years of age) with retinitis pigmentosa and hearing impairment were examined with full-field electroretinography (ERG) during general anesthesia, ophthalmologic examination, and genetic analysis. Five children were repeatedly examined (follow-up 5-10 years) with full-field ERG under local anesthesia and in 2 children multifocal ERG and optical coherence tomography (OCT) were performed. These results were compared to full-field ERG data from 58 children without retinal eye disorder. RESULTS: Six children were genotyped as Usher 1B, 2A, and 3A. Full-field ERG demonstrated early alterations corresponding to a rod-cone dystrophy in all children. A remaining rod function could be verified in the majority of the children up to 4 years of age. After 4 years of age, there was a further deterioration of the rod function; the progress was severe in Usher types 1 and 2 and moderate in Usher type 3. In all children, the cone function was moderately reduced, in a few cases almost normal. The results from the 58 children without retinal disorder confirm that full-field ERG during general anesthesia is reliable. Multifocal ERG confirmed a preserved central cone function and in OCT there were discrete structural alterations. CONCLUSIONS: Full-field ERG during general anesthesia in children with Usher syndrome demonstrates variable phenotypes and different degrees in rate of progression during childhood.