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BACKGROUND AND OBJECTIVES: In spinocerebellar ataxia, ataxia onset can be preceded by mild clinical manifestation, cerebellar and/or brainstem alterations, or biomarker modifications. READISCA is a prospective, longitudinal observational study of patients with spinocerebellar ataxia type 1 (SCA1) and 3 (SCA3) to provide essential markers for therapeutic interventions. We looked for clinical, imaging, or biological markers that are present at an early stage of the disease. METHODS: We enrolled carriers of a pathologic ATXN1 or ATXN3 expansion and controls from 18 US and 2 European ataxia referral centers. Clinical, cognitive, quantitative motor, neuropsychological measures and plasma neurofilament light chain (NfL) measurements were compared between expansion carriers with and without ataxia and controls. RESULTS: We enrolled 200 participants: 45 carriers of a pathologic ATXN1 expansion (31 patients with ataxia [median Scale for the Assessment and Rating of Ataxia: 9; 7-10] and 14 expansion carriers without ataxia [1; 0-2]) and 116 carriers of a pathologic ATXN3 expansion (80 patients with ataxia [7; 6-9] and 36 expansion carriers without ataxia [1; 0-2]). In addition, we enrolled 39 controls who did not carry a pathologic expansion in ATXN1 or ATXN3. Plasma NfL levels were significantly higher in expansion carriers without ataxia than controls, despite similar mean age (controls: 5.7 pg/mL, SCA1: 18.0 pg/mL [p < 0.0001], SCA3: 19.8 pg/mL [p < 0.0001]). Expansion carriers without ataxia differed from controls by significantly more upper motor signs (SCA1 p = 0.0003, SCA3 p = 0.003) and by the presence of sensor impairment and diplopia in SCA3 (p = 0.0448 and 0.0445, respectively). Functional scales, fatigue and depression scores, swallowing difficulties, and cognitive impairment were worse in expansion carriers with ataxia than those without ataxia. Ataxic SCA3 participants showed extrapyramidal signs, urinary dysfunction, and lower motor neuron signs significantly more often than expansion carriers without ataxia. DISCUSSION: READISCA showed the feasibility of harmonized data acquisition in a multinational network. NfL alterations, early sensory ataxia, and corticospinal signs were quantifiable between preataxic participants and controls. Patients with ataxia differed in many parameters from controls and expansion carriers without ataxia, with a graded increase of abnormal measures from control to preataxic to ataxic cohorts. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT03487367.

Background: Neonatal brachial plexus palsy remains a frequent condition and most of those patients often present active and passive joint limitation depending of the extend of the palsy. The aim of this study was to compare during the Mallet score tasks the upper limb kinematics of those patients with a reference database of non-involved arms but also to characterize kinematics changes according to the extent of the palsy., Methods: Kinematic analysis was performed using an electromagnetic device. The point of achievement position and the range of motion were analyzed. The involved arm of thirty-three patients was studied. Several groups of patients were defined depending on the level of the palsy: a C5-C8 ± T1 group (fifteen patients), a C5-C6 group (five patients) and a C5-C7 group (thirteen patients). Data from non-involved arm of thirty patients were used as control., Findings: Many significant differences were found between the control and palsy groups and between the latter. When comparing the C5-C8 ± T1 and proximal groups, for all except the mouth task, at point of achievement the scapula was more in protraction and glenohumeral elevation was lower. Elbow flexion range of motion was different for all except the external rotation task, with a decreased flexion for mouth, neck and spine tasks and a higher flexion for elevation task. For mouth task, the C5-C8 ± T1 group had a lower supination range of motion than the proximal group., Interpretation: This study helps to better understand the effect of the palsy on the humerothoracic, scapulothoracic, glenohumeral and elbow kinematics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to characterize hereditary spastic paraplegias (HSP) patients' urodynamic profiles and development of bladder symptoms., Methods: This is a multicentric retrospective study which included patients presenting with bladder disorders. We reviewed medical and urodynamic records in individuals with HSP and recorded age at onset of gait and bladder disorders, disability stage at the time of urodynamic assessment., Results: We included 122 participants. They were mostly men (n = 74) with a median age at interview of 54.6 ± 13.0 [25-76] years. The underlying genetic cause was identified in 70% of participants, with 54 heterozygous mutations in SPAST, followed by 7 SPG11 and 6 SPG7. The age at onset of motor disorder was significantly younger than for the beginning of bladder dysfunction (49.3 vs. 29.7 years-old, p < 0.001). Detrusor overactivity was present in most participants (72.1%), followed by detrusor-sphincter-dyssynergia (65.3%). Similar proportions were present in the SPAST group as well as the non-SPAST group. The SPAST group developed urinary symptoms later than the non-SPAST group as compared to the age at onset of spasticity (53.8 ± 11.3 and 44.1 ± 13.2 for the SPAST group vs. 44.1 ± 13.2 and 25.5 ± 17.3 for the non-SPAST group)., Conclusion: We have shown that the most common urodynamic pattern in HSP is detrusor overactivity associated with detrusor-sphincter dyssynergia, as would be expected for upper motor neuron lesions. We assessed the temporal window of onset, showing that urinary disorders are secondary to spastic gait in HSP and particularly frequent when walking capability deteriorates., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction: Osteogenesis imperfecta (OI) is a rare genetic bone disorder, mainly caused by autosomal dominant mutations of the COL1A1 or COL1A2 genes that encode the alpha chains of type 1 collagen. In severe forms and in nonambulatory patients, for whom physical exercise is difficult, exposing the bone to mechanical stimuli by promoting movement, especially with physiotherapy and mobility aids, is an essential part of clinical practice. However, the effects of mechanical stimulation at the cellular level remain unknown for this disease., Hypothesis: The study hypothesis was that human mesenchymal stem cells (hMSCs) from patients with OI were as sensitive to mechanical stimulation as those from healthy patients, validating the current clinical practice., Materials and Methods: hMSCs were harvested from 3 healthy control subjects and 3 patients with OI during an elective osteotomy of a long bone of the lower limb. The healthy and OI hMSCs were then exposed to mechanical stimuli, such as intermittent shear stress of 0, 0.7, 1.5, and 3 Pascal (Pa) at a frequency of 2.8 Hertz (Hz) for 30 min using a commercial ibidi system. The immediate early gene expression of themechanosensitive prostaglandin-endoperoxide synthase 2 (PTGS2) was examined 1 h after stimulation to determine the best level of mechanical stimulation. The expression of 7 other mechanosensitive genes was also examined for this level of mechanical stimulation after applying intermittent shear stress at 1.5 Pa., Results: In all hMSCs, mechanical stimulation induced PTGS2 gene overexpression with a maximum after exposure to intermittent shear stress of 1.5 Pa and without significant differences between OI and healthy donors. Except for fibroblast growth factor 2, gene expression in OI donors was found to be significantly different from that in hMSCs not exposed to shear stress. Moreover, the relative expression associated with mechanical stimulation was not significantly different between healthy and OI donors for most other genes., Discussion: This is the first study to demonstrate that hMSCs from patients with OI are as sensitive to mechanical shear stress as those from healthy donors. The mechanical stress that resulted in the greatest change in the expression of PTGS2 in patients with OI was similar to that previously reported in the literature for healthy subjects. These findings are an important step toward further fundamental research aimed at confirming the effects of mechanical stress at the cellular level over the long term and, more importantly, toward developing clinical protocols for delivering mechanical stimuli to these patients., Level of Evidence: III; comparative case-control study., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Masson SAS.)

URINARY INCONTINENCE IN CHILDREN. Urinary incontinence in children and adolescents is most often of functional origin. Questioning and clinical examination with a bladder diary should look for underlying urological or neurological causes. The type of incontinence, daytime or nocturnal, must be specified to adapt treatments. Renal and bladder ultrasound is recommended, and urodynamic studies are not routinely used. Lifestyle advice and bowel management are prerequisites for treatment. Depending on the type of symptoms, drug treatment, pelvic floor treatment, behavioral measures or stimulation of the posterior tibial nerve can be proposed. The evolution can sometimes be slow with a significant impact on quality of life, and neurocognitive aspects need to be considered., Competing Interests: H. Simonnet déclare n’avoir aucun lien d’intérêts. P. Lallemant-Dudek déclare des interventions ponctuelles pour Ipsen et Merz, et avoir été prise en charge, à l’occasion de déplacement pour congrès, par Ipsen, AbbVie, Merz.

Management of the upper limb in children with cerebral palsy is often complex and must be carried out by a team experienced in this field. Several clinical parameters must be taken into consideration, such as higher functions, visual problems, overall upper limb function, motor control, sensitivity, presence of hemineglect or synkinesis, limb position at rest and during walking. And last but not least, a complete analysis of the upper limb is required. It is only after this exhaustive assessment - which often includes occupational therapy, physiotherapy and in some cases, video and electromyography evaluations - that a treatment indication can be discussed with the patient's family. Other than baseline treatment consisting of rehabilitation, occupational therapy and bracing, botulinum toxin injections could be an option, targeting specific muscle groups. Surgical treatments, which are often indicated in severe forms with contractures, are proposed after the patient's case is presented at a multidisciplinary meeting. These include selective neurotomy, muscle-tendon release, transfer or lengthening, and procedures on bone and joints (osteotomy, arthrodesis). LEVEL OF EVIDENCE: Expert opinion., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Phenotypic variability is a consistent finding in neurogenetics and therefore applicable to hereditary spastic paraparesis. Identifying reasons for this variability is a challenge. We hypothesized that, in addition to genetic modifiers, extrinsic factors influence variability., Objectives: Our aim was to describe the clinical variability in hereditary spastic paraparesis from the person's perspective. Our goals were to identify individual and environmental factors that influence muscle tone disorders and derive interventions which could improve spasticity., Methods: This study was based on self-assessments with questions on nominal and ordinal scales completed by participants with hereditary spastic paraparesis. A questionnaire was completed either in-person in the clinic or electronically via lay organization websites., Results: Among the 325 responders, most had SPG4/SPAST (n = 182, 56%) with a mean age at onset of 31.7 (SD 16.7) years and a mean disease duration of 23 (SD 13.6) years at the time of participation. The 2 factors identified as improving spasticity for > 50% of the responders were physiotherapy (193/325, 59%), and superficial warming (172/308, 55%). Half of the responders (n = 164, 50%) performed physical activity at least once a month and up to once a week. Participants who reported physiotherapy as effective were significantly more satisfied with ≥ 3 sessions per week. Psychologically stressful situations (246/319, 77%) and cold temperatures (202/319, 63%) exacerbated spasticity for most participants., Conclusion: Participants perceived that physiotherapy reduced spasticity and that the impact of physiotherapy on spasticity was much greater than other medical interventions. Therefore, people should be encouraged to practice physical activity at least 3 times per week. This study reported participants' opinions: in hereditary spastic paraparesis only functional treatments exist, therefore the participant's expertise is of particular importance., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Brachial plexus birth palsy remains a frequent condition and one of its treatments is to transfer the Latissimus Dorsi tendon to the infraspinatus muscle. The aim of this study was to analyse, for the first time, the three-dimensional kinematic effects of this operation on the upper limb joints during the five Mallet tasks and their correlation with clinical parameters., Methods: Kinematic analysis was performed using an electromagnetic device. An Index of Improvement taking into account the angle in preop and postop, the reproducibility and the angle of a control group was developed. Three groups of patients were analysed: sixteen patients (mean: 10,5 years) for the reproducibility, thirty children (mean: 9,5 years) for the control group and ten patients (mean: 8 years 7 months) who were operated., Findings: The humerothoracic and glenohumeral external rotations improved during the external rotation, the neck and the abduction tasks and worsened during the spine task. The glenohumeral external rotation worsened during the mouth task. The Humerothoracic abduction improved during the abduction and the neck tasks. The elbow flexion improved for the neck task. Differences were observed between patients and correlations were obtained between the Index of Improvement and clinical parameters., Interpretation: Using kinematics allows to better analyse the evolution of joint angles after the latissimus dorsi transfer. The Index of Improvement allows to quickly analyse the effect of the operation for each angle and each patient. This effect depends on clinical parameters., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Hereditary spastic paraplegias (HSPs) are a group of rare, inherited, neurological diseases characterized by broad clinical and genetic heterogeneity. Lower-limb spasticity with first motoneuron involvement is the core symptom of all HSPs. As spasticity is a syndrome and not a disease, it develops on top of other neurological signs (ataxia, dystonia, and parkinsonism). Indeed, the definition of genes responsible for HSPs goes beyond the 79 identified SPG genes. In order to avoid making a catalog of the different genes involved in HSP in any way, we have chosen to focus on the HSP with cerebellar ataxias since this is a frequent association described for several genes. This overlap leads to an intermediary group of spastic ataxias which is actively genetically and clinically studied. The most striking example is SPG7 , which is responsible for HSP or cerebellar ataxia or both. There are no specific therapies against HSPs, and there is a dearth of randomized trials in patients with HSP, especially on spasticity when it likely results from other mechanisms. Thus far, no gene-specific therapy has been developed for HSP, but emerging therapies in animal models and neurons derived from induced pluripotent stem cells are potential treatments for patients., Competing Interests: The authors declare that they have no competing interests.No competing interests were disclosed.No competing interests were disclosed., (Copyright: © 2021 Durr A et al.)

Objectives: The aim of the study was to report a subtype of dysraphism designated as myelic limited dorsal malformation (MyeLDM) and to describe its characteristics at prenatal ultrasound (US)., Methods: It was a retrospective study from 2014 to 2020 based on second-line US evaluation of patients referred to our institution for myelomeningocele (MMC). Magnetic resonance imaging and acetylcholine esterase evaluation in the amniotic fluid were also offered. Major and minor criteria for open and closed dysraphism were defined and recorded for each patient. Patients were included as MyeLDM when both criteria of closed and open dysraphism were observed in the same fetus. Correlations were obtained with the postpartum data., Results: Twenty patients fulfilled the inclusion criteria, some of them being very close to MMC, others very close to limited dorsal myeloschisis (LDM), and others lying in between. There were 13 live-born neonates and 7 terminations of pregnancy. Correlations between prenatal and postpartum data were overall very good., Conclusion: Our series describe the ultrasonographic characteristics of an intermediate type of dysraphism and suggest that there is a continuum between MMC and LDM with numerous possibilities of hybrid forms (MyeLDM) sharing characteristics of both open and closed dysraphisms., (© 2021 S. Karger AG, Basel.)

Competing Interests: Les auteurs déclarent n’avoir aucun lien d’intérêts.