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Background and purpose: There are concerns for safety regarding SARS‐CoV‐2 vaccines for patients with autoimmune neuromuscular disease. We compared daily functioning using disease‐specific patient‐reported outcome measures (PROMs) before and after SARS‐CoV‐2 vaccinations. Methods: In this substudy of a prospective observational cohort study (Target‐to‐B!), patients with myasthenia gravis (MG), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), and idiopathic inflammatory myopathy (IIM) vaccinated against SARS‐CoV‐2 were included. Surveys of daily functioning (Myasthenia Gravis Activities of Daily Living, Inflammatory Rasch‐Built Overall Disability Scale, Multifocal Motor Neuropathy Rasch‐Built Overall Disability Scale, and Health Assessment Questionnaire–Disability Index) were sent before first vaccination and every 60 days thereafter for up to 12 months. Regression models were constructed to assess differences in PROM scores related to vaccination, compared to scores unrelated to vaccination. We also assessed the proportion of patients with deterioration of at least the minimal clinically important difference (MCID) between before first vaccination and 60 days thereafter. Results: We included 325 patients (median age = 59 years, interquartile range = 47–67, 156 [48%] female sex), of whom 137 (42%) had MG, 79 (24%) had CIDP, 43 (13%) had MMN, and 66 (20%) had IIM. PROM scores related to vaccination did not differ from scores unrelated to vaccination. In paired PROMs, MCID for deterioration was observed in three of 49 (6%) MG patients, of whom none reported a treatment change. In CIDP, MCID for deterioration was observed in eight of 29 patients (28%), of whom two of eight (25%) reported a treatment change. Conclusions: SARS‐CoV‐2 vaccination had no effect on daily functioning in patients with autoimmune neuromuscular diseases, confirming its safety in these patients. [ABSTRACT FROM AUTHOR]

The flower perianth has various, non‐mutually exclusive functions, such as visual signalling to pollinators and protecting the reproductive organs from the elements and from florivores, but how different perianth structures and their different sides play a role in these functions is unclear. Intriguingly, in many species there is a clear colour difference between the different sides of the perianth, with colour patterns or pigmentation present on only one side. Any adaptive benefit from such colour asymmetry is unclear, as is how the asymmetry evolved. In this viewpoint paper, we address the phenomenon of flowers with differently coloured inner and outer perianth sides, focusing on petals of erect flowers. Guided by existing literature and our own observations, we delineate three non‐mutually exclusive evolutionary hypotheses that may explain the factors underlying differently coloured perianth sides. The pollen‐protection hypothesis predicts that the outer side of petals contributes to protect pollen against UV radiation, especially during the bud stage. The herbivore‐avoidance hypothesis predicts that the outer side of petals reduces the flower's visibility to herbivores. The signalling‐to‐pollinators hypothesis predicts that flower colours evolve to increase conspicuousness to pollinators. The pollen‐protection hypothesis, the herbivore‐avoidance hypothesis, and the signalling‐to‐pollinators hypothesis generate largely but not entirely overlapping predictions about the colour of the inner and outer side of the petals. Field and laboratory research is necessary to disentangle the main drivers and adaptive significance of inner–outer petal side colour asymmetry. [ABSTRACT FROM AUTHOR]

Background: Voltage‐gated sodium channels are essential for the generation and conduction of electrical impulses in excitable cells. Sodium channel Nav1.7, encoded by the SCN9A‐gene, has been of special interest in the last decades because missense gain‐of‐function mutations have been linked to a spectrum of neuropathic pain conditions, including inherited erythermalgia (IEM), paroxysmal extreme pain disorder (PEPD), and small fiber neuropathy (SFN). Methods: In this case report, we present a 61‐year‐old woman who was referred to our tertiary referral center in a standard day care setting with suspicion of SFN. We performed additional investigations: skin biopsy to determine the intra‐epidermal nerve fiber density (IENFD), quantitative sensory testing (QST), and blood examination (including DNA analysis) for possible underlying conditions. Results: The patient showed a clinical picture that fulfilled the criteria of IEM, PEPD, and SFN. DNA analysis revealed the heterozygous variant c.554G > A in the SCN9A‐gene (OMIM 603415). This variant has already been described in all three human pain conditions separately, but never in one patient having symptoms of all three conditions. Because its pathogenicity has never been functionally confirmed, the variant is classified as a variance of unknown significance (VUS)/risk factor. This suggests that another genetic and/or environmental substrate plays a role in the development of neuropathic conditions like described. Conclusion: We have described this as the SCN9A‐pain triangle phenomenon. Treatment should focus on pain management, genetic counseling, and improving/maintaining quality of life by treating symptoms and, if indicated, starting a rehabilitation program. [ABSTRACT FROM AUTHOR]

The investigated intronic CAPN3 variant NM_000070.3:c.1746‐20C>G occurs in the Central and Eastern Europe with a frequency of >1% and there are conflicting interpretations on its pathogenicity. We collected data on 14 patients carrying the CAPN3 c.1746‐20C>G variant in trans position with another CAPN3 pathogenic/likely pathogenic variant. The patients compound heterozygous for the CAPN3 c.1746‐20C>G variant presented a phenotype consistent with calpainopathy of mild/medium severity. This variant is most frequent in the North/West regions of Russia and may originate from that area. Molecular studies revealed that different splicing isoforms are produced in the muscle. We hypothesize that c.1746‐20C>G is a hypomorphic variant with a reduction of RNA and protein expression and only individuals having a higher ratio of abnormal isoforms are affected. Reclassification of the CAPN3 variant c.1746‐20C>G from variant with a conflicting interpretation of pathogenicity to hypomorphic variant explains many unidentified cases of limb girdle muscular dystrophy R1 calpain 3‐related in Eastern and Central Europe. [ABSTRACT FROM AUTHOR]

In this retrospective study, we conducted a clinico‐genetic analysis of patients with autosomal recessive limb‐girdle muscular dystrophy (LGMD) and Miyoshi muscular dystrophy (MMD). Patients were identified at the tertiary referral centre for DNA diagnosis in the Netherlands and included if they carried two mutations in CAPN3, DYSF, SGCG, SGCA, SGCB, SGCD, TRIM32, FKRP or ANO5 gene. DNA was screened by direct sequencing and multiplex ligand‐dependent probe amplification (MLPA) analysis. A total of 244 patients was identified; 68 LGMDR1/LGMD2A patients with CAPN3 mutations (28%), 67 sarcoglycanopathy patients (LGMDR3‐5/LGMD2C‐E) (27%), 64 LGMDR12/LGMD2L and MMD3 patients with ANO5 mutations (26%), 25 LGMDR2/LGMD2B and MMD1 with DYSF mutations (10%), 21 LGMDR9/LGMD2I with FKRP mutations (9%) and one LGMDR8/LGMD2H patient with TRIM32 mutations (<1%). The estimated minimum prevalence of AR‐LGMD and MMD in the Netherlands amounted to 14.4 × 10−6. Thirty‐three novel mutations were identified. A wide range in age of onset (0‐72 years) and loss of ambulation (5‐74 years) was found. Fifteen patients (6%) initially presented with asymptomatic hyperCKemia. Cardiac abnormalities were found in 35 patients (17%). Non‐invasive ventilation was started in 34 patients (14%). Both cardiac and respiratory involvement occurs across all subtypes, stressing the need for screening in all included subtypes. [ABSTRACT FROM AUTHOR]

The objectives were to (a) assess the diagnostic value of testing clinically affected and unaffected limbs with nerve conduction studies (NCS) in patients with the asymmetric chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) variant and to define the most useful strategy for diagnosis, and (b) describe treatment response and long‐term outcome. We performed a retrospective study and included patients with a multifocal distribution of symptoms and signs, who met the probable or definite EFNS/PNS diagnostic categories for CIDP. We included 34 patients and 32 NCS datasets were available. Of these 32 patients, 25 (78%) met the electrodiagnostic criteria for definite or probable CIDP and seven (22%) for possible CIDP. Patients fulfilling the possible electrodiagnostic criteria and a supportive criterion were considered as probable CIDP. NCS of the clinically affected forearm and leg led to a probable or definite diagnosis in 13 patients (41%). Measuring both arms up to Erb's point led to a probable or definite diagnosis in 25 patients (78%), after which NCS of both legs did not contribute to additional probable or definite diagnoses. In total, 30% of patients treated with dexamethasone and 94% of patients treated with intravenous immunoglobulins (IVIg) responded. IVIg withdrawal attempts were successful in 21% of patients. After measuring the clinically affected arm up to Erb's point, NCS of the unaffected arm to Erb's point has the highest additional diagnostic yield in patients with asymmetric CIDP. Patients seem to respond better to IVIg than to corticosteroids and long‐term treatment is often required, although IVIg withdrawal was successful in 21%. [ABSTRACT FROM AUTHOR]

Introduction: The phenotype of Becker muscular dystrophy (BMD) is highly variable, and the disease may be underdiagnosed. We searched for new mutations in the DMD gene in a cohort of previously undiagnosed patients who had been referred in the period 1985-1995.Methods: All requests for DNA analysis of the DMD gene in probands with suspected BMD were re-evaluated. If the phenotype was compatible with BMD, and no deletions or duplications were detected, DNA samples were screened for small mutations.Results: In 79 of 185 referrals, no mutation was found. Analysis could be performed on 31 DNA samples. Seven different mutations, including 3 novel ones, were found. Long-term clinical follow-up is described.Conclusions: Refining DNA analysis in previously undiagnosed cases can identify mutations in the DMD gene and provide genetic diagnosis of BMD. A delayed diagnosis can still be valuable for the proband or the relatives of BMD patients. [ABSTRACT FROM AUTHOR]

This study aimed to 'define responder' through the concept of minimum clinically important differences using the individually obtained standard errors ( MCID-SE) and a heuristic 'external criterion' responsiveness method in patients with Guillain-Barré syndrome ( GBS) and chronic inflammatory demyelinating polyradiculoneuropathy ( CIDP). One hundred and fourteen newly diagnosed or relapsing patients ( GBS: 55, CIDP: 59) were serially examined (1-year follow-up). The inflammatory Rasch-built overall disability scale (I- RODS), Rasch-transformed MRC sum score ( RT-MRC), and Rasch-transformed modified- INCAT-sensory scale ( RT-mISS) were assessed. Being-a-responder was defined as having a MCID-SE cut-off ≥1.96. Also, the correlations between patients' scores on each scale and the EuroQoL health-status 'thermometer' (external criterion) were determined (higher correlation indicated better responsiveness). In both diseases, the SEs showed a characteristic 'U'-shaped dynamic pattern across each scales' continuum. The number of patients showing a meaningful change were higher for the I- RODS > RT-MRC > RT-mISS and were in GBS higher than CIDP patients. The MCID-SE concept using Rasch-transformed data demonstrated an individual pattern of 'being-a-responder' in patients with immune-mediated neuropathies, and the findings were validated by the external criterion responsiveness method. The I- RODS showed greater responsiveness compared with the MRC and INCAT-sensory scales, and its use is therefore recommended in future trials in GBS and CIDP. [ABSTRACT FROM AUTHOR]

The Jamar dynamometer and Vigorimeter have been used to assess grip strength in immune-mediated neuropathies, but have never been compared to each other. Therefore, we performed a comparison study between these two devices in patients with immune-mediated neuropathies. Grip strength data were collected in 102 cross-sectional stable and 163 longitudinal (new diagnoses or changing condition) patients with Guillain-Barré syndrome ( GBS), chronic inflammatory demyelinating polyradiculoneuropathy ( CIDP), gammopathy-related polyneuropathy ( MGUSP), and multifocal motor neuropathy ( MMN). Stable patients were assessed twice (validity/reliability studies). Longitudinal patients were assessed 3-5 times during 1 year. Responsiveness comparison between the two tools was examined using combined anchor-/distribution-based minimum clinically important difference ( MCID) techniques. Patients were asked to indicate their preference for the Jamar or Vigorimeter. Both tools correlated highly with each other (ρ = 0.86, p < 0.0001) and showed good intra-class correlation coefficients (Jamar [Right/Left hands]: ICC 0.997/0.96; Vigori: ICC 0.95/0.98). Meaningful changes were comparable between the two instruments, being higher in GBS compared to CIDP patients. In MGUSP/ MMN poor responsiveness was seen. Significant more patients preferred the Vigorimeter. In conclusion, validity, reliability, and responsiveness aspects were comparable between the Jamar dynamometer and Vigorimeter. However, based on patients' preference, the Vigorimeter is recommended in future studies in immune-mediated neuropathies. [ABSTRACT FROM AUTHOR]

We performed a comparison between Neuropathy Impairment Scale-sensory ( NISs) vs. the modified Inflammatory Neuropathy Cause and Treatment sensory scale ( mISS), and NIS-motor vs. the Medical Research Council sum score in patients with Guillain-Barré syndrome ( GBS), chronic inflammatory demyelinating polyradiculoneuropathy ( CIDP), and IgM monoclonal gammopathy of undetermined significance-related polyneuropathy ( MGUSP). The ordinal data were subjected to Rasch analyses, creating Rasch-transformed ( RT)-intervals for all measures. Comparison between measures was based on validity/reliability with an emphasis on responsiveness (using the patient's level of change related to the individually obtained varying SE for minimum clinically important difference). Eighty stable patients ( GBS: 30, CIDP: 30, and MGUSP: 20) were assessed twice (entry: two observers; 2-4 weeks later: one observer), and 137 newly diagnosed or relapsing patients ( GBS: 55, CIDP: 59, and IgM-MGUSP: 23) were serially examined with 12 months follow-up. Data modifications were needed to improve model fit for all measures. The sensory and motor scales demonstrated approximately equal and acceptable validity and reliability scores. Responsiveness scores were poor but slightly higher in RT-mISS compared to RT-NISs. Responsiveness was equal for the RT-motor scales, but higher in GBS compared to CIDP; responsiveness was poor in patients with MGUSP, suggesting a longer duration of follow-up in the latter group of patients. [ABSTRACT FROM AUTHOR]

ABSTRACT Environmental shifts and life-history changes may result in formerly adaptive traits becoming non-functional or maladaptive. In the absence of pleiotropy and other constraints, such traits may decay as a consequence of neutral mutation accumulation or selective processes, highlighting the importance of natural selection for adaptations. A suite of traits are expected to lose their adaptive function in asexual organisms derived from sexual ancestors, and the many independent transitions to asexuality allow for comparative studies of parallel trait maintenance versus decay. In addition, because certain traits, notably male-specific traits, are usually not exposed to selection under asexuality, their decay would have to occur as a consequence of drift. Selective processes could drive the decay of traits associated with costs, which may be the case for the majority of sexual traits expressed in females. We review the fate of male and female sexual traits in 93 animal lineages characterized by asexual reproduction, covering a broad taxon range including molluscs, arachnids, diplopods, crustaceans and eleven different hexapod orders. Many asexual lineages are still able occasionally to produce males. These asexually produced males are often largely or even fully functional, revealing that major developmental pathways can remain quiescent and functional over extended time periods. By contrast, for asexual females, there is a parallel and rapid decay of sexual traits, especially of traits related to mate attraction and location, as expected given the considerable costs often associated with the expression of these traits. The level of decay of female sexual traits, in addition to asexual females being unable to fertilize their eggs, would severely impede reversals to sexual reproduction, even in recently derived asexual lineages. More generally, the parallel maintenance versus decay of different trait types across diverse asexual lineages suggests that neutral traits display little or no decay even after extended periods under relaxed selection, while extensive decay for selected traits occurs extremely quickly. These patterns also highlight that adaptations can fix rapidly in natural populations of asexual organisms, in spite of their mode of reproduction. [ABSTRACT FROM AUTHOR]

Background and purpose We assessed the first evaluation at a large ventilation clinic in the Netherlands to: (i) determine what proportion of patients with motor neuron disease would benefit from earlier referral; and (ii) examine the patient preferences regarding ventilatory support. Methods Observational study at a single centre with a catchment area of 7.6 million inhabitants. Data on disease status, the referral process and patients' preferences regarding ventilatory support were collected during the first home ventilation services ( HVS) assessment and analysed for correlation with the presence of daytime hypercapnia and suspected nocturnal hypoventilation. The latter conditions require immediate (within 48 h) or subacute (within 3 weeks) initiation of ventilatory support. Results Vital capacity (in percentage of predicted value, VC%pred) was assessed by referring physicians in 84% of the 217 referred patients; the mean VC%pred was 69% ( SD 16). One-hundred and ninety-one patients attended the first HVS assessment without ventilatory support, at a median of 21 days following referral: 18% had respiratory failure (daytime hypercapnia), 19% had normocapnia but were suspected of nocturnal hypoventilation, and 63% had normocapnia without symptoms. Following the HVS assessment, 25 patients (13%) declined home mechanical ventilation; this occurred more often in patients with (14/70) compared with patients without respiratory impairment (11/121; P < 0.05). Conclusion A meaningful proportion of patients who desire ventilatory support are referred to a ventilation clinic after already developing respiratory failure. Future studies could examine means, including more sensitive respiratory measures, to detect those patients who could benefit from earlier referral. [ABSTRACT FROM AUTHOR]

Point mutations in PMP22 are relatively rare and the phenotype may vary from mild hereditary neuropathy with liability to pressure palsies (HNPP) to severe Charcot-Marie-Tooth type 1 (CMT1). We describe the phenotype of the Gly94fsX222 mutation in the PMP22 gene. Medical records of all patients were reviewed and 11 patients were re-examined. EMG was carried out in nine patients and nerve biopsy in one. Thirteen patients originating from seven families with a Gly94fsX222 mutation were included and consisted of 10 women and 3 men with a median age of 41 years (range 7-67). Five index patients were originally suspected of CMT1. Ten patients had abnormal motor skills during childhood. Nine patients had a history of pressure palsies. Involvement of the olfactory, trigeminal, facial, and pudendal nerves occurred in three patients. Twelve patients had pes cavus and one scoliosis. Distal anterior leg and distal arm weakness were found in 12 and 4 patients, respectively. Twelve patients had distal leg sensory abnormalities. Electrophysiological examination revealed a demyelinating sensorimotor neuropathy, both resembling CMT1 and HNPP. Sural nerve biopsy showed demyelinating neuropathy with presence of tomacula. More than three-fourths of the patients with Gly94fsX222 mutation demonstrated a CMT1 phenotype combined with transient deficits. Clinicians should test for this mutation in those patients exhibiting a generalised neuropathy combined with compressive like episodes. [ABSTRACT FROM AUTHOR]

Life-cycle assessment is an established tool for industrial ecology. An analysis of the energy use in the chemical and other energy-intensive industries is still under discussion in this field. We argue that the concept of exergy can play a role in industrial ecology, using a recent Norwegian power production policy question as illustration. The question is whether to build a standard natural gas- or a hydrogen-fired gas-turbine combined-cycle power plant to meet increased needs for electricity in Norway. Several indicators are relevant for this discussion, and we calculate three based on exergy calculations, as proposed in the literature. The indicators are exergy renewability, exergy efficiency, and environmental compatibility. We show how these indicators can be used to evaluate paths for sustainable power production in two gas-fired combined-cycle power plants. We found that the two plants in question were equivalent, as judged by their exergy renewability and their environmental compatibility, but not by their exergy efficiency. This indicator favored the standard power plant, possibly in combination with carbon dioxide (CO2) sequestration in a depleted gas reservoir. The analysis suggested that the present situation for power production in gas-fired combined-cycle power plants is such that one may have to choose in general between power production with a high exergy efficiency, but low renewability indicator, or the opposite, low exergy efficiency and high renewability indicator. The general importance of exergy analysis was demonstrated by this example. It enables communication between different professional groups. The technological details, understood by the engineers, can be transposed to meaningful aggregated indicators for decision makers. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which is concerned with the case of a 27 year old man with an X-linked adrenomyeloneuropathy due to a novel missense mutation in the ABCD1 start codon which presented as a demyelinating neuropathy.