In Duchenne muscular dystrophy (DMD), it is still to be determined if specific timepoints can be identified during the natural evolution of respiratory dysfunction from childhood to adulthood and if scoliosis, steroid therapy and nocturnal noninvasive mechanical ventilation (NIMV) have any effect on it.In a 7-year retrospective study performed on 115 DMD patients (6–24 years), evaluated once or twice per year, with 574 visits in total, evolution mean curves of spirometry, lung volumes, spontaneous breathing and thoraco-abdominal pattern (measured by optoelectronic plethysmography) parameters were obtained by nonlinear regression model analysis.While predicted values of forced vital capacity, forced expiratory volume in 1 s, and peak expiratory flow decline continuously since childhood, during spontaneous breathing the following parameters become significantly different than normal in sequence: abdominal contribution to tidal volume (lower after 14.8 years), tidal volume (lower after 17.2 years), minute ventilation (lower after 18.1 years) and respiratory rate (higher after 22.1 years). Restrictive lung pattern and diaphragmatic impairment are exacerbated by scoliosis severity, slowed by steroids treatment and significantly affected by NIMV.Spirometry, lung volumes, breathing pattern and thoraco-abdominal contributions show different evolution curves over time. Specific timepoints of respiratory impairment are identified during disease progression. These should be considered when defining outcome measures in clinical trials and treatment strategies in DMD.

Reliable recognition of pain is difficult in ferrets as many currently available parameters are non-specific, inconsistent and/or impractical. Grimace scales have successfully been applied to assess pain in different animal species and might also be applicable to ferrets. To compose a Ferret Grimace Scale (FGS), we studied the facial musculature of ferrets and compared lateral photographs of 19 ferret faces at six time points before and after intraperitoneal telemetry probe implantation. We identified the Action Units (AUs) orbital tightening, nose bulging, cheek bulging, ear changes and whisker retraction as potential indicators of pain in ferrets. To evaluate whether these AUs could reliably be used to identify photographs taken before and after surgery, the photographs were scored 0, 1 or 2 (not, moderately or obviously present) by 11 observers that were blinded to the treatment and timing of the photographs. All AU-scores assigned to the photographs taken five hours after surgery were significantly higher compared to their time-matched baseline scores. Further analysis using the weights that were obtained using a Linear Discriminant Analysis revealed that scoring orbital tightening alone was sufficient to make this distinction with high sensitivity, specificity and accuracy. Including weighted scores for nose bulging, cheek bulging and ear change did not change this. As these AUs had more missing values than orbital tightening, their descriptions should be re-evaluated. Including whisker retraction, which had a negative weight, resulted in lower accuracy and should therefore in its current form be left out of the FGS. Overall, the results of this study suggest that the FGS and the AU orbital tightening in particular could be useful in a multifactorial pain assessment protocol for ferrets. However, before applying the FGS in practice, it should be further validated by incorporating more time points before and after applying (different) painful stimuli, and different levels of analgesia.

Pain recognition is fundamental for safeguarding animal welfare. Facial expressions have been investigated in several species and grimace scales have been developed as pain assessment tool in many species including horses (HGS) and mice (MGS). This study is intended to progress the validation of grimace scales, by proposing a statistical approach to identify a classifier that can estimate the pain status of the animal based on Facial Action Units (FAUs) included in HGS and MGS. To achieve this aim, through a validity study, the relation between FAUs included in HGS and MGS and the real pain condition was investigated. A specific statistical approach (Cumulative Link Mixed Model, Inter-rater reliability, Multiple Correspondence Analysis, Linear Discriminant Analysis and Support Vector Machines) was applied to two datasets. Our results confirm the reliability of both scales and show that individual FAU scores of HGS and MGS are related to the pain state of the animal. Finally, we identified the optimal weights of the FAU scores that can be used to best classify animals in pain with an accuracy greater than 70%. For the first time, this study describes a statistical approach to develop a classifier, based on HGS and MGS, for estimating the pain status of animals. The classifier proposed is the starting point to develop a computer-based image analysis for the automatic recognition of pain in horses and mice.

Objective: Sporadic Creutzfeldt–Jakob disease (sCJD) comprises several subtypes as defined by genetic and prion protein characteristics, which are associated with distinct clinical and pathological phenotypes. To date, no clinical test can reliably diagnose the subtype. We established two procedures for the antemortem diagnosis of sCJD subtype using diffusion magnetic resonance imaging (MRI).Methods: MRI of 1,458 patients referred to the National Prion Disease Pathology Surveillance Center were collected through its consultation service. One neuroradiologist blind to the diagnosis scored 12 brain regions and generated a lesion profile for each MRI scan. We selected 487 patients with autopsy‐confirmed diagnosis of “pure” sCJD subtype and at least one positive diffusion MRI examination. We designed and tested two data‐driven procedures for subtype diagnosis: the first procedure—prion subtype classification algorithm with MRI (PriSCA_MRI)—uses only MRI examinations; the second—PriSCA_MRI + Gen—includes knowledge of the prion protein codon 129 genotype, a major determinant of sCJD subtypes. Both procedures were tested on the first MRI and the last MRI follow‐up.Results: PriSCA_MRI classified the 3 most prevalent subtypes with 82% accuracy.PriSCA_MRI + Gen raised the accuracy to 89% and identified all subtypes.Individually, the 2 most prevalent sCJD subtypes, MM1 and VV2, were diagnosed with sensitivities up to 95 and 97%, respectively. The performances of both procedures did not change in 168 patients with longitudinal MRI studies when the last examination was used.Interpretation: This study provides the first practical algorithms for antemortem diagnosis of sCJD subtypes. MRI diagnosis of subtype is likely to be attainable at early disease stages to prognosticate clinical course and design future therapeutic trials. ANN NEUROL 2021;89:560–572

It has been suggested that the inferior longitudinal fasciculus (ILF) may play an important role in several aspects of language processing such as visual object recognition, visual memory, lexical retrieval, reading, and specifically, in naming visual stimuli. In particular, the ILF appears to convey visual information from the occipital lobe to the anterior temporal lobe (ATL). However, direct evidence proving the essential role of the ILF in language and semantics remains limited and controversial. The first aim of this study was to prove that patients with a brain glioma damaging the left ILF would be selectively impaired in picture naming of objects; the second aim was to prove that patients with glioma infiltrating the ATL would not be impaired due to functional reorganization of the lexical retrieval network elicited by the tumor. We evaluated 48 right‐handed patients with neuropsychological testing and magnetic resonance imaging (MRI) before and after surgery for resection of a glioma infiltrating aspects of the left temporal, occipital, and/or parietal lobes; diffusion tensor imaging (DTI) was acquired preoperatively in all patients. Damage to the ILF, inferior frontal occipital fasciculus (IFOF), uncinate fasciculus (UF), arcuate fasciculus (AF), and associated cortical regions was assessed by means of preoperative tractography and pre‐/pos‐toperative MRI volumetry. The association of fascicles damage with patients' performance in picture naming and three additional cognitive tasks, namely, verbal fluency (two verbal non‐visual tasks) and the Trail Making Test (a visual attentional task), was evaluated. Nine patients were impaired in the naming test before surgery. ILF damage was demonstrated with tractography in six (67%) of these patients. The odds of having an ILF damage was 6.35 (95% CI: 1.27–34.92) times higher among patients with naming deficit than among those without it. The ILF was the only fascicle to be significantly associated with naming deficit when all the fascicles were considered together, achieving an adjusted odds ratio of 15.73 (95% CI: 2.30–178.16, p = .010). Tumor infiltration of temporal and occipital cortices did not contribute to increase the odd of having a naming deficit. ILF damage was found to be selectively associated with picture naming deficit and not with lexical retrieval assessed by means of verbal fluency. Early after surgery, 29 patients were impaired in naming objects. The association of naming deficit with percentage of ILF resection (assessed by 3D‐MRI) was confirmed (beta = −56.78 ± 20.34, p = .008) through a robust multiple linear regression model; no significant association was found with damage of IFOF, UF or AF. Crucially, postoperative neuropsychological evaluation showed that naming scores of patients with tumor infiltration of the anterior temporal cortex were not significantly associated with the percentage of ILF damage (rho = .180, p > .999), while such association was significant in patients without ATL infiltration (rho = −.556, p = .004). The ILF is selectively involved in picture naming of objects; however, the naming deficits are less severe in patients with glioma infiltration of the ATL probably due to release of an alternative route that may involve the posterior segment of the AF. The left ILF, connecting the extrastriatal visual cortex to the anterior region of the temporal lobe, is crucial for lexical retrieval on visual stimulus, such as in picture naming. However, when the ATL is also damaged, an alternative route is released and the performance improves.