Neuromuscular ultrasound standardized scanning techniques and protocols: Expert panel recommendations.

Neuromuscular ultrasound has become an integral part of the diagnostic workup of neuromuscular disorders at many centers. Despite its growing utility, uniform standard scanning techniques do not currently exist. Scanning approaches for similar diseases vary in the literature creating heterogeneity in the studies as reported in several meta-analysis. Moreover, neuromuscular ultrasound experts including the group in this study have different views with regards to technical aspects, scanning protocols, and the parameters that should be assessed. Establishing standardized neuromuscular scanning protocols is essential for the development of the subspeciality to ensure uniform clinical and research practices. Therefore, we aimed to recommend consensus-based standardized scanning techniques and protocols for common neuromuscular disorders using the Delphi approach. A panel of 17 experts participated in the study, which consisted of three consecutive electronic surveys. The first survey included voting on six scanning protocols addressing the general scanning technique and five common categories of suspected neuromuscular disorders. The subsequent surveys focused on refining the protocols and voting on new steps, rephrased statements, or areas of non-agreement. A high degree of consensus was achieved on the general neuromuscular ultrasound scanning technique and the scanning protocols for focal mononeuropathies, brachial plexopathies, polyneuropathies, amyotophic lateral sclerosis, and muscle diseases. In this study, a group of neuromuscular ultrasound experts developed six consensus-based neuromuscular ultrasound scanning protocols that may serve as references for clinicians and researchers. The standardized protocols could also aid in achieving high-quality uniform neuromuscular ultrasound practices.

Neuromuscular Ultrasound in Intensive Care Unit-Acquired Weakness: Current State and Future Directions.

Intensive care unit-acquired weakness (ICUAW) is one of the most common causes of muscle atrophy and functional disability in critically ill intensive care patients. Clinical examination, manual muscle strength testing and monitoring are frequently hampered by sedation, delirium and cognitive impairment. Many different attempts have been made to evaluate alternative compliance-independent methods, such as muscle biopsies, nerve conduction studies, electromyography and serum biomarkers. However, they are invasive, time-consuming and often require special expertise to perform, making them vastly impractical for daily intensive care medicine. Ultrasound is a broadly accepted, non-invasive, bedside-accessible diagnostic tool and well established in various clinical applications. Hereby, neuromuscular ultrasound (NMUS), in particular, has been proven to be of significant diagnostic value in many different neuromuscular diseases. In ICUAW, NMUS has been shown to detect and monitor alterations of muscles and nerves, and might help to predict patient outcome. This narrative review is focused on the recent scientific literature investigating NMUS in ICUAW and highlights the current state and future opportunities of this promising diagnostic tool.

Evaluating Diagnostic Ultrasound of the Vagus Nerve as a Surrogate Marker for Autonomic Neuropathy in Diabetic Patients.

Background and Objectives: Diagnostic ultrasound of the vagus nerve has been used to examine different polyneuropathies, and it has been suggested to be useful as a marker of autonomic dysfunction in diabetic patients. Materials and Methods: We analyzed the cross-sectional area (CSA) of the right vagus nerve of 111 patients with type 2 diabetes in comparison to 104 healthy adults and 41 patients with CIDP (chronic inflammatory demyelinating polyneuropathy). In the diabetes group, sympathetic skin response (SSR) was measured as an indicator for autonomic neuropathy. Carotid intima-media thickness (CIMT) was measured as a surrogate for atherosclerosis. Clinical symptoms of polyneuropathy were assessed using the Neuropathy Symptom Score and the Neuropathy Disability Score. Results: In total, 61.3% of the diabetes patients had clinical signs of polyneuropathy; 23.4% had no SSR at the feet as an indicator of autonomic neuropathy. Mean vagus nerve CSA did not differ in patients with and without diabetic polyneuropathy or in diabetic patients with and without SSR at the feet. No significant correlation was found between vagus nerve CSA and CIMT or SSR parameters in diabetic patients. Mean CSA of the right vagus nerve was slightly larger in diabetic patients (p = 0.028) and in patients with CIDP (p = 0.015) than in healthy controls. Conclusions: Effect sizes and mean differences were rather small so that a reliable diagnosis cannot be performed based on the vagus nerve measurement of a single person alone. Vagus nerve CSA seems not suitable as an indicator of autonomic dysfunction or cardiovascular risk in diabetic patients.

Age-Associated Characteristics of Patients With Chronic Dizziness and Vertigo.

OBJECTIVE: The incidence of dizziness and vertigo is increasing with age, and symptoms lead to significant limitations in daily living and to disability in older patients. METHOD: Data of 1,752 patients with chronic dizziness/vertigo subjected to a tertiary care, specialized interdisciplinary vertigo center were analyzed. Age, gender, symptoms, medical diagnosis, and Dizziness Handicap Inventory (DHI) were collected based on a questionnaire and analysis of associated patient records. The patients were assigned to 3 age groups (< 41, 41-65, and > 65 years). RESULTS: 33.7% of the patients were older than 65 years. Frequency of symptoms and DHI score increased with age. Older patients reported less frequently about coexisting symptoms such as nausea, headache, tinnitus, ear pressure, and visual impairment. Multisensory deficit, central vertigo, bilateral vestibulopathy, and benign paroxysmal positional vertigo were diagnosed increasingly with age, while persistent postural-perceptual dizziness and vestibular migraine were diagnosed in the younger age groups. CONCLUSION: In the diagnostic work-up of older patients age-specific characteristics of dizziness/vertigo have to be considered. The older patient generally is more impaired by the symptoms but possibly will not report typical diagnosis-defining symptoms.

Neuromuscular ultrasound competency assessment: Consensus-based survey.

Neuromuscular ultrasound is a rapidly evolving specialty with direct application for patient care. Competency assessment is an essential standard needed to ensure quality for practitioners, particularly for those newly acquiring skills with the technique. Our aim was to survey experts' opinions regarding physician competency assessment of neuromuscular ultrasound and to identify minimal competency of knowledge and skills. The opinions of 18 experts were obtained through the Delphi method using two consecutive electronic surveys. A high degree of consensus was achieved on items regarding framework and the conduct of neuromuscular ultrasound assessment and the knowledge and skills that a candidate needs to attain minimal competency in neuromuscular ultrasound. In this study, a group of neuromuscular ultrasound experts developed a general framework for neuromuscular ultrasound competency assessment and recommended testable areas of knowledge and skills suitable for establishing minimal competency.

Guidelines for neuromuscular ultrasound training.

Neuromuscular ultrasound has become an essential tool in the diagnostic evaluation of various neuromuscular disorders, and, as such, there is growing interest in neuromuscular ultrasound training. Effective training is critical in mastering this modality. Our aim was to develop consensus-based guidelines for neuromuscular ultrasound training courses. A total of 18 experts participated. Expert opinion was sought through the Delphi method using 4 consecutive electronic surveys. A high degree of consensus was achieved with regard to the general structure of neuromuscular ultrasound training; the categorization of training into basic, intermediate, and advanced levels; the learning objectives; and the curriculum for each level. In this study, a group of neuromuscular ultrasound experts established consensus-based guidelines for neuromuscular ultrasound training. These guidelines can be used in the development of the specialty and the standardization of neuromuscular ultrasound training courses and workshops.

Giant nerves in chronic inflammatory polyradiculoneuropathy.

INTRODUCTION: Nerve enlargement (NE) is described in inflammatory and inherited neuropathies. It is commonly multifocal and moderate in the former and homogeneous and generalized in the latter. We describe 4 cases of massive NE in inflammatory neuropathies. METHODS: Patients presented with symptoms of polyneuropathy that progressed over months to years. Nerve conduction studies (NCS), laboratory analysis, nerve MRI, and nerve ultrasound were performed. RESULTS: NCS revealed demyelinating neuropathy in all with multifocal conduction blocks or increased terminal latency indices. MRI/ultrasound revealed extensive NE in the roots and nerves. Detailed diagnostics including biopsies, positron emission tomography-computed tomography, and genetic testing revealed no other pathology. Chronic inflammatory demyelinating polyneuropathy variants were diagnosed in all, and immunotherapies were successfully initiated. CONCLUSIONS: MRI and ultrasound contributed to diagnosis and therapy. All patients had giant NE in common, which strongly suggested inherited neuropathy. However, the final diagnosis was inflammatory neuropathy. Impressive NE can occur in immune-mediated neuropathies and should be carefully differentiated from inherited neuropathies. Muscle Nerve 55: 285-289, 2017.

The impairment of small nerve fibers in severe sepsis and septic shock.

BACKGROUND: A decrease of small nerve fibers in skin biopsies during the course of critical illness has been demonstrated recently. However, the diagnostic use of skin biopsies in sepsis and its time course is not known. METHODS: Patients (n=32) with severe sepsis or septic shock were examined using skin biopsies, neurological examination, nerve conduction studies, and sympathetic skin response in the first week after onset of sepsis, 2 weeks and 4 months later and compared to gender- and age-matched healthy controls. RESULTS: Skin biopsies at the ankle and thigh revealed a significant decrease of intraepidermal nerve fiber density (IENFD) during the first week of sepsis and 2 weeks later. All patients developed critical illness polyneuropathy (CIP) according to electrophysiological criteria and 11 showed IENFD values lower than the 0.05 quantile. Four patients were biopsied after 4 months and still showed decreased IENFD. Results of nerve conduction studies and IENFD did considerably change over time. No differences for survival time between patients with IEFND lower and larger than 3.5 fibers/mm were found. CONCLUSIONS: Skin biopsy is able to detect an impairment of small sensory nerve fibers early in the course of sepsis. However, it may not be suited as a prognostic parameter for survival. TRIAL REGISTRATION: German Clinical Trials Register, DRKS-ID: DRKS00000642, 12/17/2010.

Nerve ultrasound in Miller Fisher variant of Guillain-Barré syndrome.

INTRODUCTION: Focal enlargement of the peripheral and spinal nerves, visualized using high-resolution ultrasound (HRUS), has been reported in early Guillain-Barré syndrome, but not in the Miller Fisher variant. We report the use of HRUS in 2 patients who presented with acute ataxic neuropathy, areflexia, and ophthalmoparesis. METHODS: Ultrasound and/or nerve conduction studies (NCS) of peripheral nerves, the vagus, and spinal nerves C5/6 were performed at onset and 2 weeks after immunoglobulin therapy. RESULTS: Both patients fulfilled criteria for diagnosis of Miller Fisher syndrome (MFS). Laboratory findings revealed elevated ganglioside Q1b antibodies in both and an albuminolocytologic dissociation in 1 patient. In addition, 1 patient had NCS evidence for demyelinating neuropathy. However, ultrasound showed focal enlargement in the vagus, the spinal nerves, and/or in the peripheral nerves in both patients. After therapy, nerve enlargement decreased in parallel with clinical improvement. CONCLUSION: Spinal and/or peripheral nerve enlargement supports the diagnosis of MFS in early phases of the disease.

Ultrasound differentiation of axonal and demyelinating neuropathies.

INTRODUCTION: Ultrasound can be used to visualize peripheral nerve abnormality. Our objective in this study was to prove whether nerve ultrasound can differentiate between axonal and demyelinating polyneuropathies (PNPs). METHODS: Systematic ultrasound measurements of peripheral nerves were performed in 53 patients (25 with demyelinating, 20 with axonal, 8 with mixed neuropathy) and 8 healthy controls. Nerve conduction studies of corresponding nerves were undertaken. RESULTS: Analysis of variance revealed significant differences between the groups with regard to motor conduction velocity, compound muscle action potential amplitude, and cross-sectional area (CSA) of different nerves at different locations. Receiver operating characteristic curve analysis revealed CSA measurements to be well suited for detection of demyelinating neuropathies, and boundary values of peripheral nerve CSA could be defined. CONCLUSIONS: Systematic ultrasound CSA measurement in different nerves helped detect demyelination, which is an additional cue in the etiological diagnosis of PNP, along with nerve conduction studies and nerve biopsy.

Ultrasonography of the peripheral nervous system in the early stage of Guillain-Barré syndrome.

Ultrasonography can be used to visualize peripheral nerve abnormalities in immune-mediated neuropathies. The objective of this study was to prove the role of ultrasonography (US) in acute phase of Guillain-Barré syndrome (GBS). Systematic ultrasonic measurements of several peripheral nerves including the vagal nerve as well as the sixth cervical nerve root were performed in 18 patients with GBS at days 1-3 after symptom onset and compared to 21 healthy controls. Nerve conduction studies (NCS) of corresponding nerves were undertaken. Consequently, significant differences between the groups were found in compound muscle action potential amplitudes, F-wave latency, and persistency. Ultrasonic cross-sectional areas (CSAs) showed significant enlargement in all nerves except of the ulnar nerve (upper arm) and the sural nerve compared to healthy controls, most prominent in proximal and middle median nerve (p < 0.01). The vagal nerve also showed enlargement compared to controls (p < 0.05), which was most pronounced in patients with autonomic dysfunction compared to patients without (p < 0.05). C6 root diameter showed a significant correlation to the amount of cerebrospinal fluid (CSF)-protein (Pearson correlation, p < 0.05). US shows nerve enlargement in several peripheral nerves including vagal nerve and C6 root in acute phase of GBS and could be an additional diagnostic tool for example, in GBS of atypical onset and autonomic dysfunction.

Acute and long-term dysphagia in critically ill patients with severe sepsis: results of a prospective controlled observational study.

Dysphagia is a major risk factor for morbidity and mortality in critically ill patients treated in intensive care units (ICUs). Structured otorhinolaryngological data on dysphagia in ICU survivors with severe sepsis are missing. In a prospective study, 30 ICU patients with severe sepsis and thirty without sepsis as control group were examined using bedside fiberoptic endoscopic evaluation of swallowing after 14 days in the ICU (T1) and 4 months after onset of critical illness (T2). Swallowing dysfunction was assessed using the Penetration-Aspiration Scale (PAS). The Functional Oral Intake Scale was applied to evaluate the diet needed. Primary endpoint was the burden of dysphagia defined as PAS score >5. At T1, 19 of 30 severe sepsis patients showed aspiration with a PAS score >5, compared to 7 of 30 in critically ill patients without severe sepsis (p = 0.002). Severe sepsis and tracheostomy were independent risk factors for severe dysphagia with aspiration (PAS > 5) at T1 (p = 0.042 and 0.006, respectively). 4-month mortality (T2) was 57 % in severe sepsis patients compared to 20 % in patients without severe sepsis (p = 0.006). At T2, more severe sepsis survivors were tracheostomy-dependent and needed more often tube or parenteral feeding (p = 0.014 and p = 0.040, respectively). Multivariate analysis revealed tracheostomy at T1 as independent risk factor for severe dysphagia at T2 (p = 0.030). Severe sepsis appears to be a relevant risk factor for long-term dysphagia. An otorhinolaryngological evaluation of dysphagia at ICU discharge is mandatory for survivors of severe critical illness to plan specific swallowing rehabilitation programs.

Uncovering sarcopenia and frailty in older adults by using muscle ultrasound-A narrative review.

Muscle ultrasound is a valuable non-invasive and cost-effective method in assessing muscle mass and structure, both of which are significant indicators for the development of sarcopenia and frailty in elderly individuals. Sarcopenia refers to the loss of muscle mass and strength that occurs with age, whereas frailty is a complex geriatric syndrome characterized by reduced physical function and an increased susceptibility to negative health outcomes. Both conditions are prevalent in older adults and are associated with higher risks of falls, disability, and mortality. By measuring muscle size and structure and several other ultrasound parameters, including muscle thickness, cross-sectional area, echogenicity (brightness in the ultrasound image), pennation angle, and fascicle length ultrasound can assist in identifying sarcopenia and frailty in older adults. In addition, ultrasound can be used to evaluate muscle function such as muscle contraction and stiffness, which may also be affected in sarcopenia and frailty. Therefore, muscle ultrasound could lead to better identification and tracking of sarcopenia and frailty. Such advancements could result in the implementation of earlier interventions to prevent or treat these conditions, resulting in an overall improvement in the health and quality of life of the elderly population. This narrative review describes the benefits and challenges when using ultra-sound for the evaluation of frailty and sarcopenia.

Perceptual plasticity is mediated by connectivity changes of the medial thalamic nucleus.

It is well known that the threshold for somatosensory perception may adapt to different inputs. Recent studies suggest the presence of a modulating effect of somatosensory inputs on the spinal dorsal horn. However, the effects of somatosensory inputs on cerebral processing and, in particular, on the functional and effective connectivity of the somatosensory brain network, are poorly understood. In this study, we investigated the longitudinal impact of somatosensory stimuli on the resting-state functional connectivity and effective connectivity of the somatosensory brain network. We performed resting-state functional magnetic resonance imaging (fMRI) in 12 healthy subjects before and after unilateral electrical median nerve stimulation. We combined this analysis with a psychophysiological examination of changes of the perception threshold. We found that the unilateral median nerve stimulation increased the perception thresholds bilaterally and increased the resting-state functional and effective connectivity between most cortical areas of the somatosensory network. The major finding, however, was a decreased resting-state functional connectivity between both secondary somatosensory cortices and the bilateral medial nuclear complex of the thalamus. This decreased connectivity was correlated with increased perception thresholds. These findings emphasize the importance of the medial thalamic nucleus for the perceptual awareness of somatosensory stimuli.

Impairment of small somatic and autonomic nerve fibres in intensive care unit patients with severe sepsis and critical illness polyneuropathy--a single center controlled observational study.

BACKGROUND: Axonal damage in large myelinated nerve fibres occurs in about 70% of patients with severe sepsis, known as critical illness polyneuropathy and contributes significantly to an increased short- and long-term morbidity and mortality in this population. Among other pathophysiological mechanisms, autonomic dysregulation, characterized by high concentrations of circulating catecholamines in the presence of impaired sympathetic modulation of heart and vessels have been discussed. We hypothesize that autonomic small fibre neuropathy play an important role in autonomic failure. METHODS/DESIGN: Single center, non-randomized, controlled, observational study. Skin biopsies of patients with severe sepsis and/or septic shock are compared with those of age-matched controls. In order to assess impairment of small nerve fibres, skin biopsies are taken at onset of severe sepsis, and two and 16 weeks later. Intraepidermal nerve fibre densities are histologically analyzed using anti protein gene product (PGP) 9.5 immunostaining. In addition, standardized clinical examinations, as Medical Research Council (MRC) scores of muscle strength, Rankin scores, and standardized nerve conduction studies of the right median nerve, the right tibial nerve, the left fibular nerve, and both sural nerves are performed, to identify critical illness polyneuropathy and to neurophysiologically quantify the damage of large nerve fibres. DISCUSSION: The study will allow to describe the frequency of small fibre neuropathy in patients with severe sepsis up to four months after onset of severe sepsis and to evaluate its relationship to critical illness polyneuropathy. TRIAL REGISTRATION: The trial has been registered to the German Clinical Trials Register. The trial registration number is DRKS-ID: DRKS00000642.

Muscle ultrasound for early assessment of critical illness neuromyopathy in severe sepsis.

INTRODUCTION: Muscle ultrasound is emerging as a promising tool in the diagnosis of neuromuscular diseases. The current observational study evaluates the usefulness of muscle ultrasound in patients with severe sepsis for assessment of critical illness polyneuropathy and myopathy (CINM) in the intensive care unit. METHODS: 28 patients with either septic shock or severe sepsis underwent clinical neurological examinations, muscle ultrasound, and nerve conduction studies on days 4 and 14 after onset of sepsis. 26 healthy controls of comparable age underwent clinical neurological evaluation and muscle ultrasound only. RESULTS: 26 of the 28 patients exhibited classic electrophysiological characteristics of CINM, and all showed typical clinical signs. Ultrasonic echogenicity of muscles was graded semiquantitatively and fasciculations were evaluated in muscles of proximal and distal arms and legs. 75% of patients showed a mean echotexture greater than 1.5, which was the maximal value found in the control group. A significant difference in mean muscle echotexture between patients and controls was found at day 4 and day 14 (both p < 0.001). In addition, from day 4 to day 14, the mean grades of muscle echotexture increased in the patient group, although the values did not reach significance levels (p = 0.085). Controls revealed the lowest number of fasciculations. In the patients group, fasciculations were detected in more muscular regions (lower and upper arm and leg) in comparison to controls (p = 0.08 at day 4 and p = 0.002 at day 14). CONCLUSIONS: Muscle ultrasound represents an easily applicable, non-invasive diagnostic tool which adds to neurophysiological testing information regarding morphological changes of muscles early in the course of sepsis. Muscle ultrasound could be useful for screening purposes prior to subjecting patients to more invasive techniques such as electromyography and/or muscle biopsy. TRIAL REGISTRATION: German Clinical Trials Register, DRKS-ID: DRKS00000642.

[Intensive care unit-acquired weakness-Diagnostic value of neuromuscular ultrasound]. / Intensive Care Unit-Acquired Weakness ­ diagnostischer Stellenwert des neuromuskulären Ultraschalls.

Intensive care unit-acquired weakness (ICUAW) is one of the most common neuromuscular complications in intensive care medicine. The clinical diagnosis and assessment of the severity using established diagnostic methods (e.g., clinical examination using the Medical Research Council Sum Score or electrophysiological examination) can be difficult or even impossible, especially in sedated, ventilated and delirious patients. Neuromuscular ultrasound (NMUS) has increasingly been investigated in ICUAW as an easy to use noninvasive and mostly patient compliance-independent diagnostic alternative. It has been shown that NMUS appears to be a promising tool to detect ICUAW, to assess the severity of muscular weakness and to monitor the clinical progression. Further studies are needed to standardize the methodology, to evaluate the training effort and to optimize outcome predication. The formulation of an interdisciplinary neurological and anesthesiological training curriculum is warranted to establish NMUS as a complementary diagnostic method of ICUAW in daily clinical practice.

Hoffmann's syndrome in the differential work-up of myopathic complaints: a case report.

BACKGROUND: Hoffmann's syndrome is a rare form of hypothyroid myopathy in adults, which is mainly characterized by muscular weakness and muscular pseudohypertrophy. CASE PRESENTATION: We report about a 61-year-old Western European man with myalgia, myxedema and pseudohypertrophy of the calf muscles. Laboratory tests revealed significantly elevated thyroid stimulating hormone (TSH) and creatine kinase (CK). Muscle MRI showed muscular hypertrophy of the lower limbs, but no signs of myositis or myopathy (no gadolinium enhancement, no edema, no fatty degeneration). In addition, electromyography (EMG) detected spontaneous activity. After the beginning of thyroxin-therapy it took six months until the muscle weakness improved and the myalgia regressed. CONCLUSIONS: Here, we focus on diagnostic routines and typical findings to differentiate Hoffmann's syndrome from other myopathies. Clinical hallmarks of Hoffmann's syndrome are pseudohypertrophy and weakness of the calf muscles in combination with elevated CK and elevated TSH. EMG is well suited to detect the involvement of the muscles and muscle MRI helps to differentiate it from other myopathies. Hoffmann's syndrome is a rare myopathy due to hypothyroidism and plays a role in the differential diagnosis of myopathic complaints even if hypothyroidism has not been detected before.