Chronic Pain in Patients with Spinal Muscular Atrophy in Switzerland: A Query to the Spinal Muscular Atrophy Registry.

Background and Objectives: Chronic pain is a common symptom in various types of neuromuscular disorders. However, for patients with spinal muscular atrophy (SMA), the literature regarding chronic pain is scarce. Thus, this study assessed the prevalence of chronic pain in children, adolescents, and adults with SMA and investigated the influence of clinical characteristics on chronic pain. Materials and Methods: This study used data from 141 patients, which were collected by the Swiss Registry for Neuromuscular Disorders. Extracted data included information on pain (present yes/no, pain location, and pain medication) and clinical characteristics, such as SMA type, motor function, wheelchair use, scoliosis, and contractures. Results: The analyses revealed that the highest prevalence of chronic pain was observed in adolescents with 62%, followed by adults with 48%, children (6-12 years) with 39%, and children < 6 years with 10%. The legs, back, and hips were most frequently reported as pain locations. Sex (females), age (adolescents), and the presence of contractures and scoliosis (with surgery) were factors that were associated with chronic pain. Conclusions: These findings contribute to a better understanding of pain in SMA, shedding light on its prevalence and characteristics in different age groups, which underscores the importance of assessing and managing pain in patients with SMA.

RevCore thrombectomy system for treatment of chronic left external and common iliac vein stent occlusion.

In recent years, deep venous stenting has increasingly become a treatment strategy for post-thrombotic syndrome. Stent thrombosis can occur, resulting in symptom recurrence despite medical therapy, and there are few options available for durable stent patency restoration. We present a case of a 50-year-old male with prior iliocaval reconstruction that experienced recurrent left lower extremity swelling secondary to occlusion of left external iliac and common iliac vein stents during follow-up. Mechanical thrombectomy with the RevCore System and angioplasty was performed. One month later, the patient demonstrated widely patent bilateral iliac vein stents and complete symptomatic resolution. The RevCore System is a feasible alternative for treatment of chronic in-stent thrombosis.

Nocturnal vestibular stimulation using a rocking bed improves a severe sleep disorder in a patient with mitochondrial disease.

Mitochondrial diseases are rare genetic disorders often accompanied by severe sleep disorders. We present the case of a 12-year-old boy diagnosed with a severe primary mitochondrial disease, exhibiting ataxia, spasticity, progressive external ophthalmoplegia, cardiomyopathy and severely disrupted sleep, but no cognitive impairment. Interestingly, his parents reported improved sleep during night train rides. Based on this observation, we installed a rocking bed in the patient's bedroom and performed different interventions, including immersive multimodal vestibular, kinesthetic and auditory stimuli, reminiscent of the sensory experiences encountered during train rides. Over a 5-month period, we conducted four 2-week nocturnal interventions, separated by 1-week washout phases, to determine the subjectively best-perceived stimulation parameters, followed by a final 4-week intervention using the optimal parameters. We assessed sleep duration and quality using the Mini Sleep Questionnaire, monitored pulse rate changes and used videography to document nocturnal interactions between the patient and caregivers. Patient-reported outcome measures, clinical examinations and personal outcomes of specific interests were used to document daytime sleepiness, restlessness, anxiety, fatigue, cognitive performance and physical posture. In the final 4-week intervention, sleep duration increased by 25%, required caregiver interactions reduced by 75%, and caregiving time decreased by 40%. Subjective fatigue, assessed by the Checklist Individual Strength, decreased by 40%, falling below the threshold of severe fatigue. Our study suggests that rocking beds could provide a promising treatment regime for selected patients with persistent severe sleep disorders. Further research is required to validate these findings in larger patient populations with sleep disorders and other conditions.

Extensive iliofemoral and femoropopliteal venous thrombosis in a young patient with iliocaval atresia.

Inferior vena cava (IVC) atresia is a rare congenital anomaly. Standardized treatment is not well defined due to its uncommon presentation, with this pathology associated with an increased risk of unprovoked lower extremity deep vein thrombosis (DVT). We present a case of a 32-year-old man who was admitted for bilateral lower extremity edema and pain and was found to have bilateral extensive iliofemoral and femoropopliteal DVT, absence of IVC filling, and extensive tortuous collateralization arising from the pelvic veins to the azygos vein. Bilateral mechanical thrombectomy and endovascular iliocaval reconstruction was performed. Three months later, the patient demonstrated widely patent iliocaval stents and the absence of DVT. Endovascular treatment of IVC atresia is feasible and optimizes the reduction of thrombus burden.

The Impact of Colonialism on Surgical Training Structures in Africa Part 1: Contextualizing the Past, Present, and Future.

Since the first African country attained independence from colonial rule, surgical training on the continent has evolved along 3 principal models. The first is a colonial, local master-apprentice model, the second is a purely local training model, and the third is a collegiate intercountry model. The 3 models exist currently and there are varied perceptions of their relative merits in training competent neurosurgeons. We reviewed the historical development of training and in an accompanying study, seek to describe the complex array of surgical training pathways and explore the neocolonial underpinnings of how these various models of training impact today the development of surgical capacity in Africa. In addition, we sought to better understand how some training systems may contribute to the widely recognized "brain drain" of surgeons from the African continent to high income countries in Europe and North America. To date, there are no published studies evaluating the impact of surgical training systems on skilled workforce emigration out of Africa. This review aims to discover potentially addressable sources of improving healthcare and training equity in this region.

The Impact of Colonialism on Surgical Training Structures In Africa Part 2: Surveying Current and Past Trainees.

BACKGROUND: As a result of gradual independence from colonial rule over the course of the past century, Africa has developed and evolved 3 primary surgical training structures: an extracontinental colonial model, an intracontinental college-based model, and several smaller national or local models. There is consistent evidence of international brain drain of surgical trainees and an unequal continental distribution of surgeons; however there has not, to date, been an evaluation of the impact colonialism on the evolution of surgical training on the continent. This study aims to identify the etiologies and consequences of this segmentation of surgical training in Africa. METHODS: This is a cross-sectional survey of the experience and perspectives of surgical training by current African trainees and graduates. RESULTS: A surgeon's region of residence was found to have a statistically significant positive association with that of a surgeon's training structure (P <0.001). A surgeon's professional college or structure of residency has a significantly positive association with desire to complete subspecialty training (P = 0.008). College and structure of residency also are statistically significantly associated with successful completion of subspecialty training (P < 0.001). CONCLUSIONS: These findings provide evidence to support the concept that the segmentation of surgical training structures in Africa, which is the direct result of prior colonization, has affected the distribution of trainees and specialists across the continent and the globe. This maldistribution of African surgical trainees directly impacts patient care, as the surgeon-patient ratios in many African countries are insufficient. These inequities should be acknowledged addressed and rectified to ensure that patients in Africa receive timely and appropriate surgical care.

Raney: a ubiquitous neurosurgical eponym.

Prior to the 1937 invention of the Raney clip, surgeons relied on hemostatic sutures, pneumatic tourniquets, sequentially applied hemostatic forceps, and the administration of local vasoconstrictive agents to achieve scalp hemostasis. The Raney clip is now the quintessential tool for achieving scalp hemostasis in cranial neurosurgery; with nearly 13.8 million cranial neurosurgical cases per year globally, Raney clips are in high demand and their use is ubiquitous. What is less known, however, is the story of their invention and the related stories of those who bear the Raney name. This paper fills these gaps in neurosurgical history, using information obtained during an extensive series of contemporary interviews and correspondence with the Raney family.

0.05% Chlorhexidine Gluconate Irrigation in Trauma/Emergency General Surgical Laparotomy Wounds Closure: A Pilot Study.

INTRODUCTION: Patients who undergo exploratory laparotomy (EL) in an emergent setting are at higher risk for surgical site infections (SSIs) compared to the elective setting. Packaged Food and Drug Administration-approved 0.05% chlorhexidine gluconate (CHG) irrigation solution reduces SSI rates in nonemergency settings. We hypothesize that the use of 0.05% CHG irrigation solution prior to closure of emergent EL incisions will be associated with lower rates of superficial SSI and allows for increased rates of primary skin closure. METHODS: A retrospective observational study of all emergent EL whose subcutaneous tissue were irrigated with 0.05% CHG solution to achieve primary wound closure from March 2021 to June 2022 were performed. Patients with active soft-tissue infection of the abdominal wall were excluded. Our primary outcome is rate of primary skin closure following laparotomy. Descriptive statistics, including t-test and chi-square test, were used to compare groups as appropriate. A P value <0.05 was statistically significant. RESULTS: Sixty-six patients with a median age of 51 y (18-92 y) underwent emergent EL. Primary wound closure is achieved in 98.5% of patients (65/66). Bedside removal of some staples and conversion to wet-to-dry packing changes was required in 27.3% of patients (18/66). We found that most of these were due to fat necrosis. We report no cases of fascial dehiscence. CONCLUSIONS: In patients undergoing EL, intraoperative irrigation of the subcutaneous tissue with 0.05% CHG solution is a viable option for primary skin closure. Further studies are needed to prospectively evaluate our findings.

Impact of Cochlear Dose on Hearing Preservation Following Stereotactic Radiosurgery in Treatment of Vestibular Schwannomas: A Multi-Center Study.

OBJECTIVE: Stereotactic radiosurgery (SRS) is a well-established treatment for vestibular schwannomas (VS). Hearing loss remains a main morbidity of VS and its treatments, including SRS. The effects of radiation parameters of SRS on hearing remain unknown. The goal of this study is to determine the effect of tumor volume, patient demographics, pretreatment hearing status, cochlear radiation dose, total tumor radiation dose, fractionation, and other radiotherapy parameters on hearing deterioration. METHODS: Multicenter retrospective analysis of 611 patients who underwent SRS for VS from 1990-2020 and had pre- and post-treatment audiograms. RESULTS: Pure tone averages (PTAs) increased and word recognition scores (WRSs) decreased in treated ears at 12-60 months while remaining stable in untreated ears. Higher baseline PTA, higher tumor radiation dose, higher maximum cochlear dose, and usage of single fraction resulted in higher post radiation PTA; WRS was only predicted by baseline WRS and age. Higher baseline PTA, single fraction treatment, higher tumor radiation dose, and higher maximum cochlear dose resulted in a faster deterioration in PTA. Below a maximum cochlear dose of 3 Gy, there were no statistically significant changes in PTA or WRS. CONCLUSIONS: Decline of hearing at one year in VS patients after SRS is directly related to maximum cochlear dose, single versus 3-fraction treatment, total tumor radiation dose, and baseline hearing level. The maximum safe cochlear dose for hearingtbrowd preservation at one year is 3 Gy, and the use of 3 fractions instead of one fraction was better at preserving hearing.

Treatment of spinal muscular atrophy with Onasemnogene Abeparvovec in Switzerland: a prospective observational case series study.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare neuromuscular disorder leading to early death in the majority of affected individuals without treatment. Recently, targeted treatment approaches including Onasemnogene Abeparvovec (OA) were introduced. This study describes the first real-world experience with OA in Switzerland. METHODS: Prospective observational case series study using data collected within the Swiss Registry for Neuromuscular Disorders from SMA patients treated with OA. Development of motor, bulbar and respiratory function, appearance of scoliosis, and safety data (platelet count, liver function, and cardiotoxicity) were analyzed. RESULTS: Nine individuals were treated with OA and followed for 383 ± 126 days: six SMA type 1 (of which two with nusinersen pretreatment), one SMA type 2, and two pre-symptomatic individuals. In SMA type 1, CHOP Intend score increased by 28.1 from a mean score of 20.5 ± 7.6 at baseline. At end of follow-up, 50% of SMA type 1 patients required nutritional support and 17% night-time ventilation; 67% developed scoliosis. The SMA type 2 patient and two pre-symptomatically treated individuals reached maximum CHOP Intend scores. No patient required adaptation of the concomitant prednisolone treatment, although transient decrease of platelet count and increase of transaminases were observed in all patients. Troponin-T was elevated prior to OA treatment in 100% and showed fluctuations in 57% thereafter. CONCLUSIONS: OA is a potent treatment for SMA leading to significant motor function improvements. However, the need for respiratory and especially nutritional support as well as the development of scoliosis must be thoroughly evaluated in SMA type 1 patients even in the short term after OA treatment.

Effects of the COVID-19 Pandemic on Access to Education and Social Participation in Children and Adolescents with Duchenne Muscular Dystrophy in Switzerland.

Two-thirds of patients with Duchenne muscular dystrophy (DMD) have cognitive and neuropsychiatric problems. Concerning their quality of life, negative factors are the lack of qualifying education and social participation in sporting and leisure activities. Adapted assistance in education and participation in social life are thus important. During the coronavirus disease 2019 (COVID-19) pandemic, the pediatric population was less severely impacted by the disease, but by the restrictions associated. The aim of this study was to evaluate the impact of the COVID-19 pandemic regarding access to education and social participation for young patients with DMD in Switzerland. We conducted a survey study from May to August 2021 assessing the impact of the COVID-19 pandemic on access to education and social participation in 8 to 18 years old patients with DMD in Switzerland. Of 60 sent surveys, 40 were returned and included. Mean age of participants was 13.5 years (±3.1 standard deviation); 23/40 of the participants were wheelchair bound, 21/40 attended a special school, and 19/40 a regular school. Of the 22/40 participants receiving assistance at school, 7/40 reported a change caused by the pandemic: for 5/7, the assistance was paused. Of the 12 boys and adolescents attending sporting activities, 10 had to suspend these. Nine attended other leisure activities; for 3/9, these activities were paused. The COVID-19 pandemic had direct effects on school assistance, sporting, and leisure activities in young patients with DMD in Switzerland. It is important to ensure that school assistance and leisure activities are rapidly resumed.

Endovascular repair of traumatic axillary artery transection associated with scapulothoracic dissociation complicated by stent separation.

We report the case of a 23-year-old female pedestrian who had been struck by a car and had presented with axillary artery transection in the setting of scapulothoracic dissociation. The initial endovascular repair was compromised by her shoulder instability and had required the addition of bridging stent placement. Caution is advised with endovascular repair in this clinical scenario because of possible stent separation.

Short-Term Outcomes After Retrograde Versus Antegrade Crossing Approaches for Femoropopliteal Occlusive Disease.

OBJECTIVE: To compare short- and mid-term outcomes of patients with femoropopliteal (FP) occlusive disease treated with a retrograde vs antegrade crossing strategy. BACKGROUND: Few studies have directly compared procedural details and outcomes after retrograde vs antegrade crossing of FP lesions. METHODS: Patients undergoing retrograde approaches to FP lesions were identified from the multicenter Excellence in Peripheral Artery Disease (XLPAD) registry between 2007 and 2015. These patients were matched 1:1 to patients treated with antegrade crossing strategies based on age, gender, comorbidities, indication for procedure, and lesion characteristics. Technical success, major adverse limb events (MALEs), and overall device cost were compared between retrograde and antegrade-only crossing. RESULTS: A total of 116 patients (58 antegrade and 58 retrograde) were included. The retrograde group had higher prevalence of coronary artery disease and presence of chronic total occlusions. The retrograde approach was associated with significantly longer procedural time (186 ± 70 minutes vs 124.4 ± 60 minutes; P<.001), but similar technical success (91.4% vs 96.6%; P=.24). There was no significant difference in perioperative morbidity. Patients treated with a retrograde approach had a lower total amputation rate (8.6% vs 22.4%; P=.04) and no difference in overall mortality (8.6% vs 5.2%; P=.47). Mean procedural costs were similar in the antegrade and retrograde groups. CONCLUSION: In patients with similar disease characteristics, a retrograde approach to FP occlusive disease was associated with longer procedural time, but improved limb salvage, without significant difference in procedural cost.

Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial.

BACKGROUND: Risdiplam is an orally administered therapy that modifies pre-mRNA splicing of the survival of motor neuron 2 (SMN2) gene and is approved for the treatment of spinal muscular atrophy. The FIREFISH study is investigating the safety and efficacy of risdiplam in treated infants with type 1 spinal muscular atrophy versus historical controls. The primary endpoint of part 2 of the FIREFISH study showed that infants with type 1 spinal muscular atrophy attained the ability to sit without support for at least 5 s after 12 months of treatment. Here, we report on the safety and efficacy of risdiplam in FIREFISH part 2 over 24 months of treatment. METHODS: FIREFISH is an ongoing, multicentre, open-label, two-part study. In FIREFISH part 2, eligible infants (aged 1-7 months at enrolment, with a genetically confirmed diagnosis of spinal muscular atrophy, and two SMN2 gene copies) were enrolled in 14 hospitals in ten countries across Europe, North America, South America, and Asia. Risdiplam was orally administered once daily at 0·2 mg/kg for infants between 5 months and 2 years of age; once an infant reached 2 years of age, the dose was increased to 0·25 mg/kg. Infants younger than 5 months started at 0·04 mg/kg (infants between 1 month and 3 months old) or 0·08 mg/kg (infants between 3 months and 5 months old), and this starting dose was adjusted to 0·2 mg/kg once pharmacokinetic data were available for each infant. The primary and secondary endpoints included in the statistical hierarchy and assessed at month 12 have been reported previously. Here we present the remainder of the secondary efficacy endpoints that were included in the statistical hierarchy at month 24: the ability to sit without support for at least 30 s, to stand alone, and to walk alone, as assessed by the Bayley Scales of Infant and Toddler Development, third edition gross motor subscale. These three endpoints were compared with a performance criterion of 5% that was defined based on the natural history of type 1 spinal muscular atrophy; the results were considered statistically significant if the lower limit of the two-sided 90% CI was above the 5% threshold. FIREFISH is registered with ClinicalTrials.gov, NCT02913482. Recruitment is closed; the 36-month extension period of the study is ongoing. FINDINGS: Between March 13 and Nov 19, 2018, 41 infants were enrolled in FIREFISH part 2. After 24 months of treatment, 38 infants were ongoing in the study and 18 infants (44% [90% CI 31-58]) were able to sit without support for at least 30 s (p<0·0001 compared with the performance criterion derived from the natural history of untreated infants with type 1 spinal muscular atrophy). No infants could stand alone (0 [90% CI 0-7]) or walk alone (0 [0-7]) after 24 months of treatment. The most frequently reported adverse event was upper respiratory tract infection, in 22 infants (54%); the most common serious adverse events were pneumonia in 16 infants (39%) and respiratory distress in three infants (7%). INTERPRETATION: Treatment with risdiplam over 24 months resulted in continual improvements in motor function and achievement of developmental motor milestones. The FIREFISH open-label extension phase will provide additional evidence regarding long-term safety and efficacy of risdiplam. FUNDING: F Hoffmann-La Roche.

European Neuromuscular Centre consensus statement on anaesthesia in patients with neuromuscular disorders.

BACKGROUND AND PURPOSE: Patients with neuromuscular conditions are at increased risk of suffering perioperative complications related to anaesthesia. There is currently little specific anaesthetic guidance concerning these patients. Here, we present the European Neuromuscular Centre (ENMC) consensus statement on anaesthesia in patients with neuromuscular disorders as formulated during the 259th ENMC Workshop on Anaesthesia in Neuromuscular Disorders. METHODS: International experts in the field of (paediatric) anaesthesia, neurology, and genetics were invited to participate in the ENMC workshop. A literature search was conducted in PubMed and Embase, the main findings of which were disseminated to the participants and presented during the workshop. Depending on specific expertise, participants presented the existing evidence and their expert opinion concerning anaesthetic management in six specific groups of myopathies and neuromuscular junction disorders. The consensus statement was prepared according to the AGREE II (Appraisal of Guidelines for Research & Evaluation) reporting checklist. The level of evidence has been adapted according to the SIGN (Scottish Intercollegiate Guidelines Network) grading system. The final consensus statement was subjected to a modified Delphi process. RESULTS: A set of general recommendations valid for the anaesthetic management of patients with neuromuscular disorders in general have been formulated. Specific recommendations were formulated for (i) neuromuscular junction disorders, (ii) muscle channelopathies (nondystrophic myotonia and periodic paralysis), (iii) myotonic dystrophy (types 1 and 2), (iv) muscular dystrophies, (v) congenital myopathies and congenital dystrophies, and (vi) mitochondrial and metabolic myopathies. CONCLUSIONS: This ENMC consensus statement summarizes the most important considerations for planning and performing anaesthesia in patients with neuromuscular disorders.

Rituximab in juvenile myasthenia gravis-an international cohort study and literature review.

Juvenile myasthenia gravis (JMG) is a rare, antibody-mediated disorder of the neuromuscular junction. Treatment strategies in JMG are largely informed by adult MG treatments as the pathophysiology is similar. Rituximab is increasingly considered as a treatment option in refractory JMG but has not yet been systematically investigated in this patient group We conducted a retrospective study from five international centres with expertise in paediatric myasthenia. 10 JMG patients treated with rituximab were identified. Following rituximab treatment all patients had a reduction in JMG-related hospital admissions. At 24 month follow up, 6 patients (60%) had achieved complete stable remission or pharmacological remission and 7 patients were able to reduce immunomodulatory treatment(s). The main side-effect was infusion-related reactions (30%) which resolved in all patients with symptomatic treatment. We compared our cohort to previously reported JMG cases treated with rituximab and noted similar response rates but a slightly higher side-effect profile. Rituximab is a safe and effective treatment option in moderate to severe JMG and most patients have an improvement in MG symptoms post treatment.

Changes in ventilation distribution in children with neuromuscular disease using the insufflator/exsufflator technique: an observational study.

Patients with neuromuscular disease often suffer from weak and ineffective cough resulting in mucus retention and increased risk for chest infections. Different airway clearance techniques have been proposed, one of them being the insufflator/exsufflator technique. So far, the immediate physiological effects of the insufflator/exsufflator technique on ventilation distribution and lung volumes are not known. We aimed to describe the immediate effects of the insufflator/exsufflator technique on different lung volumes, forced flows and ventilation distribution. Eight subjects (age 5.8-15.2 years) performed lung function tests including spirometry, multiple breath washout and electrical impedance tomography before and after a regular a chest physiotherapy session with an insufflator/exsufflator device. Forced lung volumes and flows as well as parameters of ventilation distribution derived from multiple breath washout and electrical impedance tomography were compared to assess the short-term effect of the therapy. In this small group of stable paediatric subjects with neuromuscular disease we could not demonstrate any short-term effects of insufflation/exsufflation manoeuvres on lung volumes, expiratory flows and ventilation distribution. With the currently used protocol of the insufflation/exsufflation manoeuvre, we cannot demonstrate any immediate changes in lung function.

Heterozygous frameshift variants in HNRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy.

Missense variants in RNA-binding proteins (RBPs) underlie a spectrum of disease phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, and inclusion body myopathy. Here, we present ten independent families with a severe, progressive muscular dystrophy, reminiscent of oculopharyngeal muscular dystrophy (OPMD) but of much earlier onset, caused by heterozygous frameshift variants in the RBP hnRNPA2/B1. All disease-causing frameshift mutations abolish the native stop codon and extend the reading frame, creating novel transcripts that escape nonsense-mediated decay and are translated to produce hnRNPA2/B1 protein with the same neomorphic C-terminal sequence. In contrast to previously reported disease-causing missense variants in HNRNPA2B1, these frameshift variants do not increase the propensity of hnRNPA2 protein to fibrillize. Rather, the frameshift variants have reduced affinity for the nuclear import receptor karyopherin ß2, resulting in cytoplasmic accumulation of hnRNPA2 protein in cells and in animal models that recapitulate the human pathology. Thus, we expand the phenotypes associated with HNRNPA2B1 to include an early-onset form of OPMD caused by frameshift variants that alter its nucleocytoplasmic transport dynamics.