The anterior branch of the medial femoral cutaneous nerve innervates the anterior knee: a randomized volunteer trial.

BACKGROUND: The midline skin incision for total knee arthroplasty may be an important generator of chronic neuropathic pain. The incision is innervated by the medial femoral cutaneous nerve (MFCN), the intermediate femoral cutaneous nerves (IFCN) and the infrapatellar branch from the saphenous nerve. The MFCN divides into an anterior (MFCN-A) and a posterior branch (MFCN-P). The primary aim was to compare the areas anesthesized by MFCN-A versus MFCN-P block for coverage of the incision. METHODS: Nineteen healthy volunteers had IFCN and saphenous nerve blocks. The subgroup of volunteers with a non-anesthetized gap between the areas anesthetized by the saphenous and the IFCN blocks was defined as the study group for the primary outcome. Subsequently selective MFCN-A block and MFCN block (MFCN-A + MFCN-P) were performed to investigate the contributions from MFCN-A and MFCN-P to the innervation of the midline incision. All assessments were performed blinded. RESULTS: Ten out of 19 volunteers had a non-anesthetized gap. Nine out of these 10 volunteers had coverage of the non-anesthetized gap after selective anesthesia of the MFCN-A, whereas anesthesia of the MFCN-P did not contribute to coverage of the gap in any of the 10 volunteers. CONCLUSIONS: In half of the cases, a gap of non-anesthetized skin was present on the surgical midline incision after anesthesia of the saphenous nerve and the IFCN. This gap was covered by selective anesthesia of the MFCN-A without contribution from MFCN-P. The selective MFCN-A block may be relevant for diagnosis and interventional management of neuropathic pain due to injury of MFCN-A.

Prevalence and Burden of Migraine in Switzerland: Cross-Sectional Study in ten Specialised Headache Centres from the BECOME Study.

INTRODUCTION: There is limited real-world evidence on the burden of migraine among patients with prior preventive treatment failure (PPTF). In the BECOME Swiss subanalysis, we aimed to assess current prevalence of PPTF in patients with migraine seen at specialised headache centres in Switzerland and burden of migraine in these patients. Furthermore, we assessed this burden in subgroups stratified by monthly migraine days (MMDs) and number of PPTFs. METHODS: BECOME was a prospective, multicentre, non-interventional two-part study conducted in 17 countries across Europe and Israel. This subanalysis includes patients visiting ten headache specialist centres in Switzerland. In part 1, patients visiting the centres over 3 months were screened by physicians for frequency of PPTF, MMD and other migraine characteristics. Patients with ≥ 1 PPTF and ≥ 4 MMDs were invited to take part in part 2. The primary endpoint was the proportion of patients with ≥ 1 PPTF (part 1). Other endpoints included proportion of patients specified by number of PPTF and MMD (part 1, part 2), and impact of migraine on patient-reported outcomes (PROs; part 2). RESULTS: Patients (1677) from ten Swiss centres were included in part 1, of which 855 (51.0%) reported ≥ 1 PPTF. One hundred fifty-five patients were included in part 2: 6.5% reported ≥ 4 PPTFs and 43.2% reported ≥ 15 MMDs. Mean EuroQoL 5 and EuroQoL visual analogue scale (EQ-VAS) were 0.8 ± 0.2 and 69.6 ± 20.2, respectively, suggesting a mild level of impairment in the daily functioning and self-reported health of the patients. Mean six-item Headache Impact Test (HIT-6) and modified Migraine Disability Assessment (mMIDAS) scores were 63.3 ± 6.5 and 22.7 ± 21.8, respectively, corresponding to severe migraine burden. Patients also reported impairment in work-related productivity and general activities (48.6 ± 22.8) but no associations of anxiety (7.2 ± 4.4) or depression (6.0 ± 4.4) with migraine were noted. Burden of migraine increased with increasing frequency of PPTF and MMD. CONCLUSIONS: Migraine-related quality of life, as well as work productivity are significantly affected in Swiss patients with migraine. Increasing migraine burden is associated with increasing migraine frequency and prior treatment failures.

Swiss QUality of life and healthcare impact Assessment in a Real-world Erenumab treated migraine population (SQUARE study): interim results.

BACKGROUND: The fully human monoclonal antibody erenumab, which targets the calcitonin gene-related peptide (CGRP) receptor, was licensed in Switzerland in July 2018 for the prophylactic treatment of migraine. To complement findings from the pivotal program, this observational study was designed to collect and evaluate clinical data on the impact of erenumab on several endpoints, such as quality of life, migraine-related impairment and treatment satisfaction in a real-world setting. METHODS: An interim analysis was conducted after all patients completed 6 months of erenumab treatment. Patients kept a headache diary and completed questionnaires at follow up visits. The overall study duration comprises 24 months. RESULTS: In total, 172 adults with chronic or episodic migraine from 19 different sites across Switzerland were enrolled to receive erenumab every 4 weeks. At baseline, patients had 16.6 ± 7.2 monthly migraine days (MMD) and 11.6 ± 7.0 acute migraine-specific medication days per month. After 6 months, erenumab treatment reduced Headache Impact Test (HIT-6™) scores by 7.7 ± 8.4 (p < 0.001), the modified Migraine Disability Assessment (mMIDAS) by 14.1 ± 17.8 (p < 0.001), MMD by 7.6 ± 7.0 (p < 0.001) and acute migraine-specific medication days per month by 6.6 ± 5.4 (p < 0.001). Erenumab also reduced the impact of migraine on social and family life, as evidenced by a reduction of Impact of Migraine on Partners and Adolescent Children (IMPAC) scores by 6.1 ± 6.7 (p < 0.001). Patients reported a mean effectiveness of 67.1, convenience of 82.4 and global satisfaction of 72.4 in the Treatment Satisfaction Questionnaire for Medication (TSQM-9). In total, 99 adverse events (AE) and 12 serious adverse events (SAE) were observed in 62 and 11 patients, respectively. All SAE were regarded as not related to the study medication. CONCLUSIONS: Overall quality of life improved and treatment satisfaction was rated high with erenumab treatment in real-world clinical practice. In addition, the reported impact of migraine on spouses and children of patients was reduced. TRIAL REGISTRATION: BASEC ID 2018-02,375 in the Register of All Projects in Switzerland (RAPS).

Confusion and Hallucination in a Geriatric Patient. Pitfalls of a Rare Differential: Case Report of an Anti-LGI1-Encephalitis.

Background: Confusion and hallucinations in geriatric patients are frequent symptoms and typically associated with delirium, late-life psychosis or dementia syndromes. A far rarer but well-established differential in patients with rapid cognitive deterioration, acute psychosis, abnormal movements and seizures is autoimmune encephalitis. Exemplified by our case we highlight clinical and economic problems arising in management of geriatric patients with cognitive decline and psychotic symptoms. Case Presentation: A 77-year-old female caucasian patient with an unremarkable medical history was hospitalized after a fall in association with diarrhea and hyponatremia. Upon adequate therapy, disorientation and troubled short-term memory persisted. Within a week the patient developed visual hallucinations. Basic blood and urine samples and imaging (cranial computed tomography and magnetic resonance imaging) were unremarkable. With progressive cognitive decline, amnestic impairment, word finding difficulty and general apathy, psychiatric and neurologic expertise was introduced. Advanced diagnostics did not resolve a final diagnosis; an electroencephalogram showed unspecific generalized slowing. Extended clinical observation revealed visual hallucinations and faciobrachial dystonic seizures. A treatment with anticonvulsants was initiated. Cerebrospinal fluid ultimately tested positive for voltage-gated potassium channel LGl1 (leucine-rich-inactivated-1) antibodies confirming diagnosis of autoimmune anti-LGI1 encephalitis. Immediate immunotherapy (high-dose glucocorticoids and administration of intravenous immunoglobulin G) led to a rapid improvement of the patient's condition. After immunotherapy was tapered, the patient had one relapse and completely recovered with reintroduction of glucocorticoids and initiation of therapy with rituximab. Conclusion: Rapidly progressive dementia in geriatric patients demands a structured and multidisciplinary diagnostic approach. Accurate management and financially supportable care is a major issue in rare diseases such as anti-LGI1-encephalitis. Education and awareness about autoimmune encephalitis of all physicians treating a geriatric population is important in order to involve expertise and establish treatment within reasonable time.

Pediatric Emergencies in Helicopter Emergency Medical Services: A National Population-Based Cohort Study From Denmark.

STUDY OBJECTIVE: To examine the diagnostic pattern, level of severity of illness or injuries, and mortality among children for whom a physician-staffed helicopter emergency medical service (HEMS) was dispatched. METHODS: Population-based cohort study including patients aged less than 16 years treated by the Danish national HEMS from October 1, 2014, to September 30, 2018. Diagnoses were retrieved from inhospital medical records, and the severity of illness or injuries was assessed by a severity score on scene, administration of advanced out-of-hospital care, need for intensive care in a hospital, and mortality. RESULTS: In total, 651 HEMS missions included pediatric patients aged less than 1 year (9.2%), 1 to 2 years (29.0%), 3 to 7 years (28.3%), and 8 to 15 years (33.5%). A third of the patients had critical emergencies (29.6%), and for 20.1% of the patients, 1 or more out-of-hospital interventions were performed: intubation, mechanical chest compressions, intraosseous vascular access, blood transfusion, chest tube insertion, and/or ultrasound examination. Among the 525 patients with hospital follow-up, the most frequent hospital diagnoses were injuries (32.2%), burns (11.2%), and respiratory diseases (7.8%). Within 24 hours of the mission, 18.1% of patients required intensive care. Twenty-nine patients (5.1%, 95% confidence interval [CI] 3.6 to 7.3) died either on or within 1 day of the mission, and the cumulative 30-day mortality was 35 of 565 (6.2%, 95% CI 4.5 to 8.5) (N=565 first-time missions). CONCLUSION: On Danish physician-staffed HEMS missions, 1 in 5 pediatric patients required advanced out-of-hospital care. Among hospitalized patients, nearly one-fifth of the patients required immediate intensive care and 6.2% died within 30 days of the mission.

Comparison of electrodiagnosis, neurosonography and MR neurography in localization of ulnar neuropathy at the elbow.

INTRODUCTION: In patients with ulnar neuropathy at the elbow (UNE) the precise determination of the site of lesion is important for subsequent differential diagnostic considerations and therapeutic management. Due to a paucity of comparable data, to better define the role of different diagnostic tests, we performed the first prospective study comparing the diagnostic accuracy of short segment nerve stimulation, nerve ultrasonography, MR neurography (MRN), and diffusion tensor imaging (DTI) in patients with UNE. METHODS: UNE was clinically diagnosed in 17 patients with 18 affected elbows. For all 18 affected elbows in patients and 20 elbows in 10 healthy volunteers, measurements of all different diagnostic tests were performed at six anatomical positions across the elbow with measuring points from distal (D4) to proximal (P6) in relation to the medial epicondyle (P0). Additional qualitative assessment regarding structural changes of surrounding nerve anatomy was conducted. RESULTS: The difference between affected arms of patients and healthy control arms were most frequently the largest at measure intervals D2 to P0 and P0 to P2 for electrophysiological testing, or measure points P0 and P2 for all other devices, respectively. At both levels P0 and at P2, T2 contrast-to-noise ratio (CNR) of MRN and mean diffusivity (MD) of DTI-based MRN showed best accuracies. DISCUSSION: This study revealed differences in diagnostic performance of tests concerning a specific location of UNE, with better results for T2 contrast to noise ratio (CNR) in MRN and mean diffusivity of DTI-based MRN. Additional testing with MRN and nerve ultrasonography is recommended to uncover anatomical changes.

Long-Term Effects of Self-Administered Transcranial Direct Current Stimulation in Episodic Migraine Prevention: Results of a Randomized Controlled Trial.

BACKGROUND: Migraine is a multifactorial neurovascular disorder, which affects about 12% of the general population. In episodic migraine, the visual cortex revealed abnormal processing, most likely due to decreased preactivation level. Transcranial direct current stimulation (tDCS) is able to modify cortical excitability and might result in an alleviation of migraine occurrence if used repetitively. OBJECTIVE: To test the hypothesis that self-administered anodal tDCS over the visual cortex significantly decreases the number of monthly migraine days in episodic migraine. MATERIALS AND METHODS: The study was single-blind, randomized, and sham-controlled. Inclusion criteria were age 18-80 years and an ICHD-3 diagnosis of episodic migraine. Exclusion criteria were pregnancy, presence of a neurodegenerative disorder, a contraindication against MRI examinations, and less than two migraine days during the 28-day baseline period. Patients in whom the baseline period suggested chronic migraine were excluded. After baseline, participants applied daily either verum (anodal-1 mA to 20 min) or sham tDCS (anodal-1 mA to 30 sec) at Oz (reference Cz electrode) for 28 days. Headache diaries were used to record the number of migraine days at baseline, during the stimulation period, and during four subsequent 28-day periods. RESULTS: Twenty-eight patients were included; two were excluded after the baseline period because less than two migraine days occurred; three were excluded because their headache diaries suggested the diagnosis of chronic migraine. Twenty-three datasets were taken for further analysis. Compared to sham tDCS (n = 12), verum tDCS (n = 11) resulted in a lower number of migraine days (p = 0.010) across all follow-up periods. We found no significant change in total headache days (p = 0.165), anxiety (p = 0.884), or depression scores (p = 0.535). No serious adverse events occurred; minor side effects were similar in both groups. CONCLUSIONS: This study provides Class II evidence that self-administered anodal tDCS over the visual cortex in episodic migraine results in a significantly lower number of monthly migraine days. However, it has neither an immediate nor a long-term effect.

Characterizing cognitive-motor impairments in patients with myotonic dystrophy type 1.

Myotonic Dystrophy Type 1 (DM1) is the most frequent hereditary, adult-onset muscular dystrophy. Nevertheless, DM1-associated cognitive-motor impairments have not been fully characterized so far. This study aimed at profiling cognitive and locomotor dysfunctions in these patients. In addition, cognitive-motor interactions were assessed using a dual-task paradigm. Comprehensive cognitive-motor impairment profiles were generated for 19 patients with DM1 and 19 healthy subjects by thorough clinical, biomechanical and neuropsychological examinations. Detailed gait analysis was performed using a 3D motion capture system, whereas cognitive function was assessed using a standardized neuropsychological test battery. Patients with DM1 showed impaired functional mobility, gait velocity and endurance. DM1-related gait pathology was mainly characterized by enhanced dynamic instability, gait variability, and restricted ankle dorsiflexion. Patients' cognitive impairments particularly concerned attentional functions. Dual-task conditions induced gait deviations that slightly differed between patients and controls. DM1-associated cognitive impairments correlated with reduced functional mobility and impaired ankle dorsiflexion. Patients with DM1 revealed significant impairments of walking function, balance and cognitive performance. Differential cognitive-motor interference and significant interactions between cognitive and motor dysfunctions point towards a prominent role of cognition in gait performance of patients with DM1.

Resistance training preserves high-intensity interval training induced improvements in skeletal muscle capillarization of healthy old men: a randomized controlled trial.

Skeletal muscle capillarization is a determining factor in gas and metabolite exchange, while its impairments may contribute to the development of sarcopenia. Studies on the potential of resistance training (RT) to induce angiogenesis in older muscles have been inconclusive, and effects of sequential endurance training (ET) and RT on capillarization are unknown. Healthy older men (66.5 ± 3.8 years) were engaged in either 12 weeks of habitual course observation (HC) followed by 12 weeks of RT (n = 8), or 12 weeks of high-intensity interval training (HIIT) followed by 12 weeks of RT (n = 9). At baseline, following 12 and 24 weeks, m. vastus lateralis biopsies were obtained. (Immuno-)histochemistry was used to assess indices of muscle fiber capillarization, muscle fiber morphology and succinate dehydrogenase (SDH) activity. Single periods of RT and HIIT resulted in similar improvements in capillarization and SDH activity. During RT following HIIT, improved capillarization and SDH activity, as well as muscle fiber morphology remained unchanged. The applied RT and HIIT protocols were thus similarly effective in enhancing capillarization and oxidative enzyme activity and RT effectively preserved HIIT-induced adaptations of these parameters. Hence, both, RT and HIIT, are valid training modalities for older men to improve skeletal muscle vascularization.

Satellite cell content in Huntington's disease patients in response to endurance training.

BACKGROUND: Skeletal muscle wasting is a hallmark of Huntington's disease (HD). However, data on myocellular characteristics and myofiber remodeling in HD patients are scarce. We aimed at gaining insights into myocellular characteristics of HD patients as compared to healthy controls at rest and after a period of increased skeletal muscle turnover. METHODS: Myosin heavy chain (MyHC)-specific cross-sectional area, satellite cell content, myonuclear number, myonuclear domain, and muscle fiber type distribution were determined from vastus lateralis muscle biopsies at rest and after 26 weeks of endurance training in HD patients and healthy controls. RESULTS: At the beginning of the study, there were no differences in myocellular characteristics between HD patients and healthy controls. Satellite cell content per MyHC-1 fiber (P = 0.014) and per MyHC-1 myonucleus (P = 0.006) increased significantly in healthy controls during the endurance training intervention, whereas it remained constant in HD patients (P = 0.804 and P = 0.975 for satellite cell content per MyHC-1 fiber and myonucleus, respectively). All further variables were not altered during the training intervention in HD patients and healthy controls. CONCLUSIONS: Similar skeletal muscle characteristics between HD patients and healthy controls at baseline suggested similar potential for myofiber remodeling in response to exercise. However, the missing satellite cell response in MyHC-1 myofibers following endurance training in HD patients points to a potential dysregulation in the exercise-induced activation and/or proliferation of satellite cells. In the longer-term, impaired myonuclear turnover might be associated with the clinical observation of skeletal muscle wasting.

Exercise in Huntington's Disease: Current State and Clinical Significance.

Background: Huntington's disease (HD) is a rare, progressive neurodegenerative disease. Currently, there is no cure for the disease, but treatment may alleviate HD symptoms. In recent years, several exercise training interventions have been conducted in HD patients. In the current article, we review previous studies investigating targeted exercise training interventions in HD patients. Methods: We performed a literature search using the PubMed, Scopus, Web of Science, and Google Scholar databases on exercise training interventions in HD patients. Six publications fulfilled the criteria and were included in the review. Results: Exercise training resulted in beneficial effects on cardiovascular and mitochondrial function. Training effects on cognition, motor function, and body composition were less congruent, but a positive effect seems likely. Health-related quality of life during the training interventions was stable. Most studies reported no related adverse events in response to training. Discussion: Exercise training seems to be safe and feasible in HD patients. However, current knowledge is mainly based on short, small-scale studies and it cannot be transferred to all HD patients. Therefore, longer-term interventions with larger HD patient cohorts are necessary to draw firm conclusions about the potentially positive effects of exercise training in HD patients.

Cutaneous anaesthesia of hip surgery incisions with iliohypogastric and subcostal nerve blockade: A randomised trial.

BACKGROUND: Cutaneous nerve blockade may improve analgesia after hip surgery. Anaesthesia after the lateral femoral cutaneous (LFC) nerve block is too distal for complete coverage of most hip surgery incisions, which requires additional anaesthesia of the adjacent, proximal area. The transversalis fascia plane (TFP) block potentially anaesthetises the iliohypogastric and subcostal nerves. The primary aim of the present study was to investigate, if the TFP block provides cutaneous anaesthesia adjacent to the LFC nerve block. METHODS: Active vs placebo TFP blocks were compared in a paired randomised controlled trial (RCT) in 20 volunteers, who all had bilateral LFC nerve blocks. The day preceding the RCT, the area anaesthetised by a novel selective ultrasound guided subcostal nerve block was identified bilaterally in order to assess the contribution of the subcostal nerve to the area anaesthesia by the TFP block. RESULTS: Anaesthesia of the lateral hip region after TFP block was 80%. The cutaneous anaesthesia after active TFP block was in continuity with the LFC nerve block in 65%. Combined TFP and LFC nerve blockade significantly increased the coverage of hip surgery incisions compared to LFC nerve block alone. The success rate of blocking the subcostal nerve was 50% with the TFP block. CONCLUSION: The TFP block anaesthetises the skin proximal to the LFC nerve block by anaesthetising the iliohypogastric and subcostal nerves. TFP block as a supplement to LFC nerve block improves the coverage of the proximal surgical incisions used for hip surgery.

Vestibulo-cochlear function in inflammatory neuropathies.

OBJECTIVE: We aimed to quantify peripheral-vestibular deficits that may contribute to imbalanced stance/gait in patients with inflammatory neuropathies. METHODS: Twenty-one patients (58 ±â€¯15 y [mean age ±â€¯1SD]; chronic-inflammatory-demyelinating-polyneuropathy = 10, Guillain-Barré Syndrome = 5, Anti-MAG peripheral neuropathy = 2, multifocal-motor-neuropathy = 4) were compared with 26 healthy controls. All subjects received video-head-impulse testing (vHIT), caloric irrigation and cervical/ocular vestibular-evoked myogenic-potentials (VEMPs). The Yardley vertigo-symptom-scale (VSS) was used to rate vertigo/dizziness. Postural stability was assessed using the functional gait-assessment (FGA). Pure-tone audiograms (n = 18), otoacoustic emissions (n = 12) and auditory brainstem responses were obtained (n = 12). RESULTS: Semicircular-canal hypofunction was noted in 9/21 (43%) patients (vHIT = 6; caloric irrigation = 5), whereas otolith function was impaired in 12/21 (57%) (oVEMPs = 8; cVEMPs = 5), resulting in vestibular impairment of at least one sensor in 13/21 (62%). On average, 2.4 ±â€¯1.1 vestibular end organs (each side: anterior/posterior/horizontal canal, utriculus, sacculus; total = 10) were affected. The VSS-scores were higher in patients (16.8 ±â€¯8.6 vs. 9.5 ±â€¯6.2, p = 0.002) but did not correlate with the number of affected organs. Auditory neuropathy was found in 1/12 (8%) patients. CONCLUSION: Impairment of one or more vestibular end organs was frequent, but usually mild, possibly contributing to imbalance of stance/gait in inflammatory neuropathies. SIGNIFICANCE: While our data does not support routine vestibular testing in inflammatory neuropathies, this may be considered in selected cases.

The Lateral Femoral Cutaneous Nerve: Description of the Sensory Territory and a Novel Ultrasound-Guided Nerve Block Technique.

BACKGROUND AND OBJECTIVES: Nerve blockade of the lateral femoral cutaneous (LFC) nerve provides some analgesia after hip surgery. However, knowledge is lacking about the extent of the cutaneous area anesthetized by established LFC nerve block techniques, as well as the success rate of anesthetic coverage of various surgical incisions. Nerve block techniques that rely on ultrasonographic identification of the LFC nerve distal to the inguinal ligament can be technically challenging. Furthermore, the branching of the LFC nerve is variable, and it is unknown if proximal LFC nerve branches are anesthetized using the current techniques. The primary aim of this study was to investigate a novel ultrasound-guided LFC nerve block technique based on injection into the fat-filled flat tunnel (FFFT), which is a duplicature of the fascia lata between the sartorius and the tensor fasciae latae muscle, in order to assess the success rate of anesthetizing the proximal LFC nerve branches and covering of the different surgical incisions used for hip surgery. METHODS: First, a cadaveric study was conducted in order to identify an FFFT injection technique that would provide adequate injectate spread to the proximal LFC nerve branches. Second, a clinical study was conducted in a group of 20 healthy volunteers over 2 consecutive days. On trial day 1, successful complete anesthesia of the LFC nerve was defined by performing a suprainguinal fascia iliaca block bilaterally in each subject. On trial day 2, a triple-blind randomized controlled trial compared the effect of the novel ultrasound-guided LFC nerve block technique for bupivacaine versus placebo. The primary end point was the success rate of anesthesia of the proximal cutaneous area innervated by the LFC nerve for the FFFT injection with bupivacaine versus placebo. RESULTS: Adequate spread of injectate to the proximal LFC nerve branches in cadavers was obtained by injecting 10 mL with dynamic needle-tip tracking in the FFFT. Application of this technique in the randomized controlled trial provided anesthesia of the lateral thigh with a success rate of 95% (95% confidence interval, 73.9%-99.8%) for the active side and 0% for placebo (P < 0.001). The proximal branches were anesthetized with a success rate of 68% (95% confidence interval, 43.4%-87.4%) on the active side. The proximal extent of the anesthetized cutaneous area was on average 7.9 cm distal to the greater trochanter. CONCLUSIONS: This novel LFC nerve block technique is easy and quick and reliably produces anesthesia of the lateral thigh. The greater trochanter is rarely included in the area of anesthesia, which reduces the coverage of each specific surgical incision. The success rate of 68% in anesthetizing the proximal nerve branches must be further evaluated by future research.

Effects of endurance training on skeletal muscle mitochondrial function in Huntington disease patients.

BACKGROUND: Mitochondrial dysfunction may represent a pathogenic factor in Huntington disease (HD). Physical exercise leads to enhanced mitochondrial function in healthy participants. However, data on effects of physical exercise on HD skeletal muscle remains scarce. We aimed at investigating adaptations of the skeletal muscle mitochondria to endurance training in HD patients. METHODS: Thirteen HD patients and 11 healthy controls completed 26 weeks of endurance training. Before and after the training phase muscle biopsies were obtained from M. vastus lateralis. Mitochondrial respiratory chain complex activities, mitochondrial respiratory capacity, capillarization, and muscle fiber type distribution were determined from muscle samples. RESULTS: Citrate synthase activity increased during the training intervention in the whole cohort (P = 0.006). There was no group x time interaction for citrate synthase activity during the training intervention (P = 0.522). Complex III (P = 0.008), Complex V (P = 0.043), and succinate cytochrome c reductase (P = 0.008) activities increased in HD patients and controls by endurance training. An increase in mass-specific mitochondrial respiratory capacity was present in HD patients during the endurance training intervention. Overall capillary-to-fiber ratio increased in HD patients by 8.4% and in healthy controls by 6.4% during the endurance training intervention. CONCLUSIONS: Skeletal muscle mitochondria of HD patients are equally responsive to an endurance-training stimulus as in healthy controls. Endurance training is a safe and feasible option to enhance indices of energy metabolism in skeletal muscle of HD patients and may represent a potential therapeutic approach to delay the onset and/or progression of muscular dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov NCT01879267 . Registered May 24, 2012.

Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and review of 76 cases.

BACKGROUND: Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset muscle disorder, characterized by the presence of nemaline rods in muscle fibers. Phenotypic characterization in a large cohort and a comprehensive overview of SLONM are lacking. METHODS: We studied the clinico-pathological features, treatment and outcome in a large cohort of 76 patients with SLONM, comprising 10 new patients and 66 cases derived from a literature meta-analysis (PubMed, 1966-2016), and compared these with 15 reported HIV-associated nemaline myopathy (HIV-NM) cases. In 6 SLONM patients, we performed a targeted next-generation sequencing (NGS) panel comprising 283 myopathy genes. RESULTS: SLONM patients had a mean age at onset of 52 years. The predominant phenotype consisted of weakness and atrophy of proximal upper limbs in 84%, of proximal lower limbs in 80% and both in 67%. Other common symptoms included axial weakness in 68%, as well as dyspnea in 55% and dysphagia in 47% of the patients. In 53% a monoclonal gammopathy of unknown significance (MGUS) was detected in serum. The mean percentage of muscle fibers containing rods was 28% (range 1-63%). In 2 cases ultrastructural analysis was necessary to detect the rods. The most successful treatment in SLONM patients (all with MGUS) was autologous peripheral blood stem cell therapy. A targeted NGS gene panel in 6 SLONM patients (without MGUS) did not reveal causative pathogenic variants. In a comparison of SLONM patients with and without MGUS, the former comprised significantly more males, had more rapid disease progression, and more vacuolar changes in muscle fibers. Interestingly, the muscle biopsy of 2 SLONM patients with MGUS revealed intranuclear rods, whereas this feature was not seen in any of the biopsies from patients without paraproteinemia. Compared to the overall SLONM cohort, significantly more HIV-NM patients were male, with a lower age at onset (mean 34 years). In addition, immunosuppression was more frequently applied with more favorable outcome, and muscle biopsies revealed a significantly higher degree of inflammation and necrosis in this cohort. Similar to SLONM, MGUS was present in half of the HIV-NM patients. CONCLUSIONS: SLONM presents a challenging, but important differential diagnosis to other neuromuscular diseases of adult onset. Investigations for MGUS and HIV should be performed, as they require distinct but often effective therapeutic approaches. Even though SLONM and HIV-NM show some differences, there exists a large clinico-pathological overlap between the 2 entities.

A Cadaveric Study of Ultrasound-Guided Subpectineal Injectate Spread Around the Obturator Nerve and Its Hip Articular Branches.

BACKGROUND AND OBJECTIVES: The femoral and obturator nerves are assumed to account for the primary nociceptive innervation of the hip joint capsule. The fascia iliaca compartment block and the so-called 3-in-1-block have been used in patients with hip fracture based on a presumption that local anesthetic spreads to anesthetize both the femoral and the obturator nerves. Evidence demonstrates that this presumption is unfounded, and knowledge about the analgesic effect of obturator nerve blockade in hip fracture patients presurgically is thus nonexistent. The objectives of this cadaveric study were to investigate the proximal spread of the injectate resulting from the administration of an ultrasound-guided obturator nerve block and to evaluate the spread around the obturator nerve branches to the hip joint capsule. METHODS: Fifteen milliliters of methylene blue was injected into the interfascial plane between the pectineus and external obturator muscles in 7 adult cadavers. The spread of the injectate into the obturator canal and around the obturator and accessory obturator nerve branches to the hip joint was evaluated by subsequent dissection. RESULTS: The injected dye spread into the obturator canal and colored all obturator branches to the hip joint capsule in all 14 sides. Furthermore, the accessory obturator nerve was present in 3 sides (21%), and the nerve and its branches to the hip joint capsule were colored in all cases. CONCLUSIONS: In cadavers, injection of 15 mL of methylene blue into the interfascial plane between the pectineus and the external obturator muscle effectively spreads proximally to reach the obturator canal, as well as the obturator nerve branches to the hip joint capsule and the accessory obturator nerve.