Illness Weakness, Polyneuropathy and Myopathy: Diagnosis, treatment, and long-term outcomes.

BACKGROUND: Severe weakness associated with critical illness (CIW) is common. This narrative review summarizes the latest scientific insights and proposes a guide for clinicians to optimize the diagnosis and management of the CIW during the various stages of the disease from the ICU to the community stage. MAIN BODY: CIW arises as diffuse, symmetrical weakness after ICU admission, which is an important differentiating factor from other diseases causing non-symmetrical muscle weakness or paralysis. In patients with adequate cognitive function, CIW can be easily diagnosed at the bedside using manual muscle testing, which should be routinely conducted until ICU discharge. In patients with delirium or coma or those with prolonged, severe weakness, specific neurophysiological investigations and, in selected cases, muscle biopsy are recommended. With these exams, CIW can be differentiated into critical illness polyneuropathy or myopathy, which often coexist. On the general ward, CIW is seen in patients with prolonged previous ICU treatment, or in those developing a new sepsis. Respiratory muscle weakness can cause neuromuscular respiratory failure, which needs prompt recognition and rapid treatment to avoid life-threatening situations. Active rehabilitation should be reassessed and tailored to the new patient's condition to reduce the risk of disease progression. CIW is associated with long-term physical, cognitive and mental impairments, which emphasizes the need for a multidisciplinary model of care. Follow-up clinics for patients surviving critical illness may serve this purpose by providing direct clinical support to patients, managing referrals to other specialists and general practitioners, and serving as a platform for research to describe the natural history of post-intensive care syndrome and to identify new therapeutic interventions. This surveillance should include an assessment of the activities of daily living, mood, and functional mobility. Finally, nutritional status should be longitudinally assessed in all ICU survivors and incorporated into a patient-centered nutritional approach guided by a dietician. CONCLUSIONS: Early ICU mobilization combined with the best evidence-based ICU practices can effectively reduce short-term weakness. Multi-professional collaborations are needed to guarantee a multi-dimensional evaluation and unitary community care programs for survivors of critical illnesses.

[Traditional Chinese therapy in the treatment of ICU-acquired weakness: a Meta-analysis].

OBJECTIVE: To systematically assess the efficacy of traditional Chinese therapy in the treatment of ICU-acquired weakness (ICU-AW). METHODS: PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP were retrieved by computer and were used to collect a randomized controlled trials (RCT) of traditional Chinese therapy for ICU-AW. The retrieval time was from databases establishment to December 2021. After 2 researchers independently screened the literature, extracted data and evaluated the risk of bias included in the study, and RevMan 5.4 software was used for Meta-analysis. RESULTS: 334 articles were selected, totally 13 clinical studies and 982 patients were included, including 562 in the trial group and 420 in the control group. Meta-analysis results showed that traditional Chinese therapy could improve clinical efficacy of ICU-AW patients [relative risk (RR) = 1.35, 95% confidence interval (95%CI) was 1.20 to 1.52, P < 0.000 01], improve the muscle strength [Medical Research Council score (MRC score); standardized mean difference (SMD) = 1.00, 95%CI was 0.67 to 1.33, P < 0.000 01], improve daily life ability [modified Barthel index score (MBI score); SMD = 1.67, 95%CI was 1.20 to 2.14, P < 0.000 01], shorten mechanical ventilation time (SMD = -1.47, 95%CI was -1.84 to -1.09, P < 0.000 01), reduce the length of intensive care unit (ICU) stay [mean difference (MD) = -3.28, 95%CI was -3.89 to -2.68, P < 0.000 01], reduce the total hospitalization time (MD = -4.71, 95%CI was -5.90 to -3.53, P < 0.000 01), reduce tumor necrosis factor-α (TNF-α; MD = -4.55, 95%CI was -6.39 to -2.70, P < 0.000 01) and interleukin-6 (IL-6; MD = -5.07, 95%CI was -6.36 to -3.77, P < 0.000 01). There was no obvious advantage in reducing the severity of the disease [acute physiology and chronic health evaluation II (APACHE II; SMD = -0.45, 95%CI was -0.92 to 0.03, P = 0.07). CONCLUSIONS: Based on the current research, traditional Chinese therapy can improve the clinical efficacy of ICU-AW, improve muscle strength and daily life ability, shorten mechanical ventilation, the length of ICU stay and total hospitalization time, reduce TNF-α and IL-6. But traditional Chinese therapy can not reduce the overall disease severity.

The combined intervention of neuromuscular electrical stimulation and nutrition therapy: A scoping review.

BACKGROUND & AIMS: Neuromuscular electrical stimulation (NMES) is a safe and appropriate complement to voluntary resistance training for muscle weakness. However, its feasibility and effectiveness in combination with nutritional therapy remains unclear. This scoping review aimed to summarize the evidence on combined interventions for individuals with or at risk of sarcopenia for guiding future relevant research. METHODS: A systematic electronic search was conducted using the following databases and registry: MEDLINE, CINAHL, Web of Science, PEDro, and ClinicalTrials. gov. Two independent reviewers summarized the characteristics, effectiveness, and feasibility of the combined intervention and the risk of bias in the literature. RESULTS: Nine RCTs and four non-RCTs involving 802 participants were eligible. A diverse group of participants were included: older adults with sarcopenic obesity, patients in intensive care, and patients with cancer. Evidence-based interventions combining NMES and nutritional therapy were tailored to each patient's underlying disease. Although most studies were of low to moderate quality, it can be suggested that combined interventions may be feasible and effective for increasing skeletal muscle mass. CONCLUSION: This scoping review demonstrates the potential of combined interventions as a new sarcopenia treatment strategy and highlights the need to examine the effects in high-quality RCTs with larger sample sizes.

Neuropatía motora multifocal: ¿cómo diagnosticar un caballo de Troya? / Multifocal motor neuropathy: how to diagnose a trojan horse?

Introducción: La neuropatía motora multifocal con bloqueos de la conducción (NMMBC) es una enfermedad crónica inmunomediada, con un compromiso exclusivo de los nervios motores. Es importante diferenciarla de otras enfermedades que cursan con afectación motora, debido a que ésta es una enfermedad tratable. Cuadro clínico: Paciente varón de 56 años, con compromiso motor progresivo en el miembro superior del lado derecho desde el año 2016. El examen neurofisiológico demostró la presencia de múltiples bloqueos de la conducción nerviosa. Los anticuerpos antigangliósidos fueron negativos. Se indicó tratamiento con inmunoglobulina endovenosa en varios ciclos, con mejoría progresiva del cuadro. Discusión: Se discute el plan diagnóstico clínico y electrofisiológico, los diagnósticos diferenciales, las hipótesis fisiopatológicas y el tratamiento de esta enfermedad de rara ocurrencia

Introduction: Multifocal motor neuropathy with conduction blocks (NMMBC) is a chronic immunemediated disease that exclusively involves the motor nerves. It is important to differentiate it from other diseases that present with motor involvement, because this is a treatable disease. Clinical picture: A 56-year-old male patient, with progressive motor involvement in the right upper limb since 2016. A neurophysiological examination revealed multiple nerve conduction blocks. Antiganglioside antibodies were negative. Treatment with intravenous immunoglobulin was indicated for several cycles with progressive improvement of the condition. Discussion: Clinical and electrophysiological diagnostic plans, differential diagnoses, pathophysiological hypotheses, and treatment of this rare disease are discussed

Congenital syphilis in a 4-month-old infant with limb weakness.

We describe a rare case of a 4-month-old girl presenting with a several month history of reduced movement to the left arm accompanied by a maculopapular rash to the limbs. X-ray findings included inflammatory periosteal changes to the radius and ulna. Treponema pallidum IgM was detected in both baby and mother, and a diagnosis of congenital syphilis was made. This case is an interesting clinical picture with a variety of important differential diagnoses, including non-accidental injury, malignancy, autoimmune disease and other congenital infections. With an increasing rate of congenital syphilis infection in the developed world, it is vital that clinicians are able to recognise symptoms to ensure prompt diagnosis and treatment. In this respect, we can attempt to avoid the chronic and potentially life-threatening complications of untreated infection.

The effect of Omega-3 polyunsaturated fatty acid supplementation on exercise-induced muscle damage.

BACKGROUND: Exercise-induced muscle damage (EIMD) results in transient muscle inflammation, strength loss, muscle soreness and may cause subsequent exercise avoidance. Omega-3 (n-3) supplementation may minimise EIMD via its anti-inflammatory properties, however, its efficacy remains unclear. METHODS: Healthy males (n = 14, 25.07 ± 4.05 years) were randomised to 3 g/day n-3 supplementation (N-3, n = 7) or placebo (PLA, n = 7). Following 4 weeks supplementation, a downhill running protocol (60 min, 65% V̇O2max, - 10% gradient) was performed. Creatine kinase (CK), interleukin (IL)-6 and tumour necrosis factor (TNF)-α, perceived muscle soreness, maximal voluntary isometric contraction (MVIC) and peak power were quantified pre, post, and 24, 48 and 72 h post-EIMD. RESULTS: Muscle soreness was significantly lower in N-3 vs PLA group at 24 h post-EIMD (p = 0.034). IL-6 was increased in PLA (p = 0.009) but not in N-3 (p = 0.434) following EIMD, however, no significant differences were noted between groups. Peak power was significantly suppressed in PLA relative to pre-EIMD but not in N-3 group at 24 h post-EIMD. However, no significant difference in peak power output was observed between groups. MVIC, CK and TNF-α were altered by EIMD but did not differ between groups. CONCLUSION: N-3 supplementation for 4 weeks may successfully attenuate minor aspects of EIMD. Whilst not improving performance, these findings may have relevance to soreness-associated exercise avoidance.

Abdominal weakness, bulge, or hernia after DIEP flaps: An algorithm of management, prevention, and surgical repair with classification.

BACKGROUND: This study analyzes abdominal weakness, hernia, and bulge following deep inferior epigastric perforator (DIEP) flap breast reconstruction. Abdominal wall morbidities are categorized, and an algorithm for management is provided. METHODS: A retrospective review of 644 patients who underwent abdominal based flap breast reconstruction between 2009 and 2018 and met selection criteria was performed. Bulge and hernia were evaluated on exam and then by imaging and/or operative exploration. The incidence of abdominal weakness was evaluated by BREAST-Q™ data. Risk factors were analyzed. RESULTS: Of the 644 patients, 23 (3.6%) had a clinically significant bulge or hernia on exam postoperatively. Developing an abdominal wound postoperatively and sacrificing nerves both correlated with an increased incidence of bulge or hernia (p < 0.05). The use of lateral row perforators, keeping the umbilicus, higher BMI, and the use of biological mesh in the initial abdominal wall repair trended toward an increased incidence of bulge or hernia; however, these data were not statistically significant. Seven percent of patients who answered the BREAST-Q™ reported abdominal weakness. Patients in the umbilicus sacrificing cohort had an increased incidence of weakness (p < 0.05). Abdominal wounds, nerve sacrificing procedures and obesity correlated with an increased incidence of weakness; these data were not statistically significant. CONCLUSIONS: A classification and algorithm for treatment of functional abdominal wall morbidity after DIEP flap is provided. Abdominal wall morbidity is classified as: type 1 - abdominal weakness; type 2 - smaller, unilateral abdominal bulge; and type 3 - true abdominal hernia or large bilateral bulge. An algorithm of treatment is presented, which includes physical therapy and surgical repair recommendations.

A Comparison of Neuromuscular Electrical Stimulation Parameters for Postoperative Quadriceps Strength in Patients After Knee Surgery: A Systematic Review.

CONTEXT: Postoperative quadriceps strength weakness after knee surgery is a persistent issue patients and health care providers encounter. OBJECTIVE: To investigate the effect of neuromuscular electrical stimulation (NMES) parameters on quadriceps strength after knee surgery. DATA SOURCES: CINAHL, MEDLINE, SPORTDiscus, and PubMed were systematically searched in December 2018. STUDY SELECTION: Studies were excluded if they did not assess quadriceps strength or if they failed to report the NMES parameters or quadriceps strength values. Additionally, studies that applied NMES to numerous muscle groups or simultaneously with other modalities/treatments were excluded. Study quality was assessed with the Physiotherapy Evidence Database (PEDro) scale for randomized controlled trials. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 1. DATA EXTRACTION: Treatment parameters for each NMES treatment was extracted for comparison. Quadriceps strength means and standard deviations were extracted and utilized to calculate Hedge g effect sizes with 95% CIs. RESULTS: Eight RCTs were included with an average Physiotherapy Evidence Database scale score of 5 ± 2. Hedge g effect sizes ranged from small (-0.37; 95% CI, -1.00 to 0.25) to large (1.13; 95% CI, 0.49 to 1.77). Based on the Strength of Recommendation Taxonomy Quality of Evidence table, the majority of the studies included were low quality RCTs categorized as level 2: limited quality patient-oriented evidence. CONCLUSION: Because of inconsistent evidence among studies, grade B evidence exists to support the use of NMES to aid in the recovery of quadriceps strength after knee surgery. Based on the parameters utilized by studies demonstrating optimal treatment effects, it is recommended to implement NMES treatment during the first 2 postoperative weeks at a frequency of ≥50 Hz, at maximum tolerable intensity, with a biphasic current, with large electrodes and a duty cycle ratio of 1:2 to 1:3 (2- to 3-second ramp).

Acupuncture for Anaemia and Large Intestine Impaction Associated with Hind Limb Weakness in a Horse: A Case Report.

A 24-year-old horse was presented with a clinical history of anaemia, large intestine impaction and hind limb weakness. Loss of body weight was also reported. Hematocrit and hemoglobin levels were low and piroplasmosis test was negative. Nasogastric intubation with laxative agents was performed and 50 ml of a red blood-cell-supplement was given daily during a month. An assessment following Traditional Chinese Veterinary Medicine (TCVM) principles was performed after the last episode of large intestine impaction. A swollen, pale and wet tongue was observed. A superficial, weak pulse combined punctually with a slippery pulse was detected on the right side. The pulse on the left side was very thin. BL18, BL20 and BL23 were the most sensitive acupoints on the right side. BL18 and BL23 were the most sensitive on the left. TCVM diagnosis was Qi/Yang Kidney Deficiency, Spleen Qi Deficiency with Stagnation and Blood Deficiency. It received acupuncture at Bai-Hui, KI3, KI7, KI10, BL23, GB39, ST36, BL17 and acupressure at SP10. The client reported a significant improvement after treatment and hematocrit and hemoglobin levels were normal. KI3, ST36, BL39 acupoints were treated 14 days later. The outcome was favourable and one acupuncture session per month was recommended. No previous case reports in equines have been documented with a combination of blood, gastrointestinal and musculoskeletal problems in the same episode. This case is an example of an integrative approach to investigate the origin and the interdependent relation between body systems.

Feasibility of eccentric overloading and neuromuscular electrical stimulation to improve muscle strength and muscle mass after treatment for head and neck cancer.

PURPOSE: Treatment of head and neck cancer (HNC) results in severe weight loss, mainly due to the loss of lean body mass. Consequently, decreases in muscular strength and health-related quality of life (HRQL) occur. This study investigated the feasibility of a 12-week novel strength training (NST) and conventional strength training (CST) intervention delivered after HNC treatment. METHODS: Participants were randomized to a NST group (n = 11) involving eccentric overloaded strength training and neuromuscular electrical stimulation (NMES), or a CST group (n = 11) involving dynamic resistance exercises matched for training volume. Feasibility outcomes included recruitment, completion, adherence, and evidence of progression. A neuromuscular assessment involving maximal isometric voluntary contractions (MIVCs) in the knee extensors was evaluated prior to and during incremental cycling to volitional exhaustion at baseline and after the interventions. Anthropometrics and patient-reported outcomes (PROs) were also assessed. RESULTS: Although recruitment was challenging, completion was 100% in NST and 82% in CST. Adherence was 92% in NST and 81% in CST. Overall, MIVC increased by 19 ± 23%, muscle cross-sectional area improved 18 ± 22%, cycling exercise time improved by 18 ± 13%, and improvements in HRQL and fatigue were clinically relevant. CONCLUSIONS: Both interventions were found to be feasible for HNC patients after treatment. Strength training significantly improved maximal muscle strength, muscle cross-sectional area, and PROs after HNC treatment. Future research should include fully powered trials and consider the use of eccentric overloading and NMES during HNC treatment. IMPLICATIONS FOR CANCER SURVIVORS: Eccentric- and NMES-emphasized strength training may be useful alternatives to conventional strength training after HNC treatment.

Long-term morbidity after a negative sentinel node in breast cancer patients.

OBJECTIVE: Morbidity after sentinel lymph node biopsy is often underestimated. The aim of this study was to inventory arm and shoulder complaints in sentinel node-negative breast cancer patients post-surgery after long-term follow-up. METHODS: Sentinel node-negative breast cancer patients with at least 2 years of follow-up after surgery were included in this study. Self-reported arm and shoulder morbidities were assessed using a survey. Patients (n = 126) were asked if they ever developed complaints, if these complaints were still present and whether they were ever treated for these complaints. RESULTS: After a mean follow-up of 55.5 months (range 25-86 months), the prevalence of the self-reported arm and shoulder complaints was 25.8% for pain, 12.0% for numbness, 6.4% for paraesthesias, 7.1% for lymphedema, 8.0% for axillary web syndrome, 26.2% for loss of strength and 19.5% for limitations in range of motion. About 38.1% of the patients were treated by a physical therapist concerning the experienced complaints after SLNB. CONCLUSION: Up to 7 years post-surgery a considerable amount of sentinel node-negative patients still suffer from arm and shoulder complaints. These complaints affect the activities of daily living. Therefore, more research is needed regarding the value of early detection and treatment of these complaints.

Blood Flow-Restricted Training for Lower Extremity Muscle Weakness due to Knee Pathology: A Systematic Review.

CONTEXT:: Blood flow-restricted training (BFRT) has been suggested to treat lower extremity muscle weakness. The efficacy of BFRT for muscle problems related to knee pathology is unclear. OBJECTIVE:: To determine whether BFRT (1) improves muscle strength and cross-sectional area (CSA) for chronic knee-related lower extremity atrophy and (2) prevents muscle atrophy after knee surgery. DATA SOURCES:: A systematic review of the literature from 1974 to 2017 was conducted using the PubMed and Cochrane databases. STUDY SELECTION:: Controlled trials that used BFRT to treat chronic knee-related lower extremity muscle atrophy or to prevent muscle atrophy after knee surgery that measured the effects on quadriceps or hamstrings muscle strength or CSA were included. STUDY DESIGN:: Systematic review. LEVEL OF EVIDENCE:: Level 2. DATA EXTRACTION:: Data were extracted as available from 9 studies (8 level 1, 1 level 2). Assessment of study quality was rated using the Physiotherapy Evidence Database or Methodological Index for Non-Randomized Studies instruments. RESULTS:: BFRT was used after anterior cruciate ligament reconstruction and routine knee arthroscopy and in patients with knee osteoarthritis or patellofemoral pain. There were a total of 165 patients and 170 controls. Vascular occlusion and exercise protocols varied; all studies except 1 incorporated exercises during occlusion, most of which focused on the quadriceps. Six of 7 studies that measured quadriceps strength reported statistically significant improvements after training. Few benefits in quadriceps CSA were reported. Hamstrings strength was only measured in 2 studies. There were no complications related to training. CONCLUSION:: Published limited data show BFRT to be safe and potentially effective in improving quadriceps muscle strength in patients with weakness and atrophy related to knee pathology. The use of short-duration vascular occlusion and light-load resistance exercises appears safe after knee surgery or in arthritic knees. This treatment option requires further investigation to refine protocols related to cuff pressure and exercise dosage and duration.

Anti-HMGCR antibody-associated necrotising myopathy and its association with statin use.

A 66-year-old man presented with chest pain and a 1-year history of generalised weakness, accompanied with generalised aches and pains. Symptoms worsened when he was initiated on statins. Investigations yielded high creatine kinase, high HMG-coenzymeA reductase (HMGCR) antibody titre, myopathic features on electromyography and muscle biopsy, and muscle atrophy on MRI. These results were in keeping with anti-HMGCR antibody myopathy. The patient responded well to immunosuppressive therapy.

A Physical and Psychological Approach to Managing Fatigue in Myasthenia Gravis: A Pilot Study.

BackgroundFatigue in myasthenia gravis (MG) is common and difficult to manage. Unlike myasthenic weakness it is not amenable to drug therapies.ObjectiveOur primary aim was to investigate whether a combination of physical and psychological therapy would help address symptoms of fatigue in MG patients, who have stable disease but residual problematic fatigue. Our secondary aim was to quantitate fatigue by applying different scores and to ascertain which would be most relevant to apply in MG.MethodsWe recruited 10 MG patients with stable disease and who suffer from fatigue. Nine of these 10 patients participated in a 10-week program that involved physical and psychological intervention. We quantified their fatigue using the modified fatigue impact scale (MFIS), the visual analogue fatigue scale (VAFS) and the fatigue severity scale (FSS) at the start of the study, at various intervals during the program and 3 months later.ResultsDuring the program, there was a small improvement in the physical and psychosocial subscale of the MFIS. There was a significant improvement (p < 0.01) in the VAFS at the end of the program. No clear improvement was noted in FSS. Three months later, all fatigue scores declined to baseline but 50% of patients had made some life-style changes.ConclusionsThis is a small pilot study, which utilized a combined approach with physical and psychological therapy, and showed some benefit in improving fatigue in patients with MG. The improvement was small and unsustained. Because of the small patient cohort, one cannot derive any firm conclusions and a larger study is required to investigate this further.

[Dropped head syndrome as first manifestation of primary hyperparathyroid myopathy].

75 years old woman presented with 6-month history of progressive dropped head syndrome. Neurological examination revealed moderate weakness of flexor and extensor of neck and mild weakness of proximal appendicular muscles with normal deep tendon reflexes. The needle electromyography showed short duration and low amplitude motor unit potential. No fibrillation potentials or positive sharp waves were seen. Biopsy of deltoid muscle was normal. Laboratory studies showed elevated levels of serum calcium (11.8 mg/dl, upper limit of normal 10.1) and intact parathyroid hormone (104 pg/ml, upper limit of normal 65), and decreased level of serum phosphorus (2.3 mg/dl, lower limit of normal 2.7). Ultrasonography and enhanced computed tomography revealed a parathyroid tumor. The tumor was removed surgically. Pathological examination proved tumor to be parathyroid adenoma. Dropped head and weakness of muscles were dramatically improved within a week after the operation. Although hyperparathyroidism is a rare cause of dropped head syndrome, neurologists must recognize hyperparathyroidism as a treatable cause of dropped head syndrome.

Neuromuscular diseases: Diagnosis and management.

Neuromuscular diseases (NMDs) affect the peripheral nervous system, which includes the motor neurons and sensory neurons; the muscle itself; or the neuromuscular junction. Thus, the term NMDs encompasses a vast array of different syndromes. Some of these syndromes are of direct relevance to paediatric orthopaedic surgeons, either because the presenting manifestation is a functional sign (e.g., toe-walking) or deformity (e.g., pes cavus or scoliosis) suggesting a need for orthopaedic attention or because orthopaedic abnormalities requiring treatment develop during the course of a known NMD. The main NMDs relevant to the orthopaedic surgeon are infantile spinal muscular atrophy (a motor neuron disease), peripheral neuropathies (chiefly, Charcot-Marie-Tooth disease), congenital muscular dystrophies, progressive muscular dystrophies, and Steinert myotonic dystrophy (or myotonic dystrophy type 1). Muscle weakness is a symptom shared by all these conditions. The paediatric orthopaedic surgeon must be familiar, not only with the musculoskeletal system, but also with many other domains (particularly respiratory and cardiac function and nutrition) that may interfere with the treatment and require preoperative management. Good knowledge of the natural history of each NMD is essential to ensure optimal timing of the therapeutic interventions, which must be performed under the best possible conditions in these usually frail patients. Timing is particularly crucial for the treatment of spinal deformities due to paraspinal muscle hypotonia during growth: depending on the disease and natural history, the treatment may involve non-operative methods or growing rods, followed by spinal fusion. A multidisciplinary approach is always required. Finally, the survival gains achieved in recent years increasingly require attention to preparing for adult life, to orthopaedic problems requiring treatment before the patient leaves the paediatric environment, and to the transition towards the adult healthcare system.

Dietary intervention rescues myopathy associated with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder with complex symptomology. In addition to a predisposition to tumors, children with NF1 can present with reduced muscle mass, global muscle weakness, and impaired motor skills, which can have a significant impact on quality of life. Genetic mouse models have shown a lipid storage disease phenotype may underlie muscle weakness in NF1. Herein we confirm that biopsy specimens from six individuals with NF1 similarly manifest features of a lipid storage myopathy, with marked accumulation of intramyocellular lipid, fibrosis, and mononuclear cell infiltrates. Intramyocellular lipid was also correlated with reductions in neurofibromin protein expression by western analysis. An RNASeq profile of Nf1null muscle from a muscle-specific Nf1 knockout mouse (Nf1MyoD-/-) revealed alterations in genes associated with glucose regulation and cell signaling. Comparison by lipid mass spectrometry demonstrated that Nf1null muscle specimens were enriched for long chain fatty acid (LCFA) containing neutral lipids, such as cholesterol esters and triacylglycerides, suggesting fundamentally impaired LCFA metabolism. The subsequent generation of a limb-specific Nf1 knockout mouse (Nf1Prx1-/-) recapitulated all observed features of human NF1 myopathy, including lipid storage, fibrosis, and muscle weakness. Collectively, these insights led to the evaluation of a dietary intervention of reduced LCFAs, and enrichment of medium-chain fatty acids (MCFAs) with L-carnitine. Following 8-weeks of dietary treatment, Nf1Prx1-/- mice showed a 45% increase in maximal grip strength, and a 71% reduction in intramyocellular lipid staining compared with littermates fed standard chow. These data link NF1 deficiency to fundamental shifts in muscle metabolism, and provide strong proof of principal that a dietary intervention can ameliorate symptoms.

[Hypercalcemic crisis and hypocalcemic tetany]. / Hyperkalzämische Krise und hypokalzämische Tetanie.

A serum calcium level >3.5 mmol/l together with clinical symptoms such as muscle weakness, fatigue, nausea, vomiting, pancreatitis or even coma are characteristic for a hypercalcemic crisis (HC). Primary hyperparathyroidism (1HPT) and malignancy-associated hypercalcemia are the most frequent causal diseases for a HC. The analysis of serum levels for calcium, phosphorous, intact parathyroid hormone, electrophoresis and renal function parameters indicate which further radiological, scintigraphic or serum diagnostic steps are adequate to identify the cause of the patient's acute situation (i. e. most frequently 1HPT or malignant disease with bone involvement, e. g. myeloma) and thus to initiate the required surgical or oncological intervention. However, the primary goals in the treatment of HC include correcting dehydration and improving kidney function, lowering calcium levels and decreasing osteoclastic bone resorption. The goals are accomplished by volume repletion, forced diuresis, antiresorptive agents and hemodialysis on an intensive care unit. Hypocalcemic tetany (HT) is the consequence of severely lowered calcium levels (<2.0 mmol/l), usually in patients with chronic hypocalcemia. The causal disease for hypocalcemic tetany is frequently a lack of parathyroid hormone (PTH), (e. g. as a complication of thyroid surgery) or, rarely, resistance to PTH. HT due to severe and painful clinical symptoms requires rapid i. v. calcium replacement by central venous catheter on an intensive care unit. For the treatment of chronic hypocalcemia oral calcium and 25OH-vitamin D or even 1,25(OH)2-vitamin D3 and magnesium supplements may be necessary to achieve the desired low normal calcium levels. Thiazides are useful to reduce renal calcium loss and to stabilize the calcium levels. Some patients continue to exhibit clinical symptoms despite adequate calcium levels; in these cases s. c. parathyroid hormone 1-84 should be considered to stabilize calcium levels and to lower the dosage of calcium and vitamin D supplements.