World Federation of Neurology.

BACKGROUND AND PURPOSE: To acknowledge the occasion of the 10th anniversary of the formation of the European Academy of Neurology (EAN), the World Federation of Neurology was invited to contribute its perspective on the formation of the EAN and its activities over the past decade. METHODS: This article is based on the experiences of the author in several functions with the European Union of Medical Specialists, the European Federation of Neurology and the European Neurological Society and with the World Federation of Neurology as a trustee since 2009. This article is supported by the author's own archive as well as by several publications. RESULTS: The formation of the EAN was influenced by the activities of the two main predecessor societies, the European Neurological Society and European Federation of Neurology, which left an imprint on the structure of the EAN. The newly formed EAN underwent rigorous structural and organizational changes and has been acting as a successful and independent regional society, expanding increasingly in worldwide activities. CONCLUSION: The EAN, with its 47 member countries, strong democratic leadership and structure, is an excellent example of a regional society with expanding global influence that uses its advocacy skills to influence and improve the structure of neurology in Europe.

Decreasing incidence of stroke, ischaemic heart disease and dementia in Norway, 1990-2019, a Global Burden of Disease study: an opportunity.

BACKGROUND AND PURPOSE: The declining incidence of stroke, ischaemic heart disease (IHD) and dementia (the 'triple threat') in Norway encourages further investigation. The risks and trends of the three conditions were analysed using data from the Global Burden of Disease study. METHODS: Global Burden of Disease 2019 estimations were used for age-, sex- and risk-factor-specific incidence and prevalence of the 'triple threat', their risk-factor-attributed deaths and disability combined, their age-standardized rates per 100,000 population in 2019 and their changes during 1990-2019. Data are presented as means and 95% uncertainty intervals. RESULTS: In 2019, 71.1 thousand Norwegians were living with dementia, 157.2 thousand with IHD and 95.2 thousand with stroke. In 2019, there were 9.9 thousand (8.5 to 11.3) new cases of dementia (35.0% increase since 1990), 17.0 thousand (14.6 to 19.6) with IHD (3.6% decrease) and 8.0 thousand (7.0 to 9.1) with stroke (12.9% decrease) in Norway. During 1990-2019, their age-standardized incidence rates decreased significantly-dementia by -5.4% (-8.4% to -3.2%), IHD by -30.0% (-31.4% to -28.6%) and stroke by -35.3% (-38.3% to -32.2%). There were significant declines in the attributable risks to both environmental and behavioural factors in Norway, but contradictory trends for metabolic risk factors during 1990-2019. CONCLUSIONS: The risk of the 'triple threat' conditions is declining in Norway, despite the increased prevalence. This offers the opportunity to find out why and how and to accelerate their joint prevention through new approaches and the promotion of the National Brain Health Strategy.

Mapping of European activities on the integration of sex and gender factors in neurology and neuroscience.

BACKGROUND: Neurological disorders pose a profound unmet medical need for which new solutions are urgently needed. The consideration of both biological (sex) and socio-cultural (gender) differences between men and women is necessary to identify more efficacious, safer and tailored treatments. Approaches for putting sex and gender medicine into practice have gathered momentum across Europe, but it is currently unclear to what extent they have been implemented in the field of neurology and neuroscience. METHODS: We mapped current activities in research, funding and education aimed at integrating sex and gender consideration in neuroscience and neurology in Europe. We examined and analyzed data gathered from (1) literature searches, (2) policy documents and reports by the European Commission and national funding agencies, (3) web-based searches, (4) "Web of Science", and (5) searches of project databases of funding agencies. An informative / non-systematic search was performed for sections on policies and funding, education, basic research, while a systematic literature and database review was conducted forquantitative analysis of research output and funded projects in terms of sex and gender analysis. RESULTS: Our mapping shows that there is a growing interest and attention towards sex and gender consideration in neurological fields, both from funding agencies and researchers. However, most activities, especially for education, are limited to the individual motivation of researchers and are not organically built within curricula and strategic research priorities. DISCUSSION: We recommend actions that might help increase the consideration of sex and gender specifically in the field of neuroscience and neurology.

Cubital tunnel perfusion in different postures-An anatomical investigation.

INTRODUCTION/AIMS: For cubital tunnel syndrome, the avoidance of predisposing arm positions and the use of elbow splints are common conservative treatment options. The rationale is to prevent excessive stretching and compression of the nerve in the cubital tunnel, as this mechanical stress impedes intraneural perfusion. Data regarding those upper extremity postures to avoid, or whether elbow flexion alone is detrimental, are inconsistent. This study aimed to assess perfusion and size changes of the cubital tunnel during different postures in an experimental cadaver setup. METHODS: Axillary arteries in 30 upper extremities of fresh cadavers were injected with ultrasound contrast agent. High-resolution ultrasound of the cubital tunnel was performed during five different arm postures that gradually increased tension on the ulnar nerve and caused cubital tunnel narrowing. Contrast enhancement within the tunnel was measured to quantify perfusion. Cubital tunnel cross-sectional area was measured to detect compression. RESULTS: Increasing tension significantly reduced perfusion. When isolated, neither shoulder elevation, elbow flexion, pronation, nor extension of wrist and fingers impaired perfusion. However, combining two or more of these postures led to significant decreases. Significant narrowing of the cubital tunnel was seen in full elbow flexion and shoulder elevation. DISCUSSION: Combinations of some upper extremity joint positions reduce nerve perfusion, but isolated elbow flexion does not have a significant impact. We hypothesize that elbow splints alone may not influence cubital tunnel perfusion but may only prevent direct compression of the ulnar nerve. Advising patients about upper extremity postures that should be avoided may be more effective.

Vancouver Declaration II on Global Headache Patient Advocacy 2019.

In 2017, the International Headache Society convened a Global Patient Advocacy Summit (GPAS-1) to begin a collaborative effort involving patients, patient advocates, patient advocacy organizations, healthcare professionals, scientists, professional pain, neurology, and headache societies, pharmaceutical manufacturers, and regulatory agencies to advance issues of importance to patients affected by headache worldwide. In September 2019, the second Global Patient Advocacy Summit (GPAS-2) was convened to revisit issues from the inaugural meeting, assess the progress of the International Headache Society Global Patient Advocacy Coalition (IHS-GPAC) in meeting the goals set forth therein, and discuss strategies for achieving established goals and supporting future development. Short- and long-term mandates from the first Summit were realized, including publishing the Vancouver Declaration on Global Headache Patient Advocacy 2018, determining the governing and operational structures of the IHS-GPAC, and helping to facilitate the first World Federation of Neurology World Brain Day dedicated to migraine. Another short-term mandate, creating a unified advocacy strategy, was fulfilled by the Coalition's decision to focus on encouraging support from employers and implementing employee support programs for people with migraine. To help execute the strategy, the Coalition is developing an employer engagement toolkit that will educate employers and employees about the impact of migraine in the workplace, reduce stigma directed toward employees with migraine, and facilitate the care of employees with migraine to reduce the burden of illness and improve workplace productivity. Coalition members will disseminate the toolkit and encourage the adoption of migraine workplace programs by employers worldwide. The Coalition has established an alliance with two global, multinational employers to expand migraine awareness and support among policy makers and other stakeholders around the world. The IHS-GPAC met many of the goals established at GPAS-1, and it has initiated a global strategy focused on the psychosocial and economic toll of headache disorders, especially migraine, in the workplace. Ongoing and future activities will explore a range of opportunities with employers and across the full spectrum of advocacy goals.

Patients' and physicians' interpretation of chemotherapy-induced peripheral neurotoxicity.

To test if and how chemotherapy-induced peripheral neurotoxicity (CIPN) is perceived differently by patients and physicians, making assessment and interpretation challenging. We performed a secondary analysis of the CI-PeriNomS study which included 281 patients with stable CIPN. We tested: (a) the association between patients' perception of activity limitation in performing eight common tasks and neurological impairment and (b) how the responses to questions related to these daily activities are interpreted by the treating oncologist. To achieve this, we compared patients' perception of their activity limitation with neurological assessment and the oncologists' blind interpretation. Distribution of the scores attributed by oncologists to each daily life maximum limitation ("impossible") generated three groups: Group 1 included limitations oncologists attributed mainly to motor impairment; Group 2 ones mainly attributed to sensory impairment and Group 3 ones with uncertain motor and sensory impairment. Only a subset of questions showed a significant trend between severity in subjective limitation, reported by patients, and neurological impairment. In Group 1, neurological examination confirmed motor impairment in only 51%-65% of patients; 76%-78% of them also had vibration perception impairment. In Group 2, sensory impairment ranged from 84% to 100%; some degree of motor impairment occurred in 43%-56% of them. In Group 3 strength reduction was observed in 49%-50% and sensory perception was altered in up to 82%. Interpretation provided by the panel of experienced oncologists was inconsistent with the neurological impairment. These observations highlight the need of a core set of outcome measures for future CIPN trials.

Hereditary transthyretin-related amyloidosis.

Hereditary transthyretin(TTR)-related amyloidosis (ATTRm amyloidosis) is an endemic/non-endemic, autosomal-dominant, early- and late-onset, rare, progressive disorder, predominantly manifesting as length-dependent, small fiber dominant, axonal polyneuropathy and frequently associated with cardiac disorders and other multisystem diseases. ATTRm amyloidosis is due to variants in the TTR gene, with the substitution Val30Met as the most frequent mutation. TTR mutations lead to destabilization and dissociation of TTR tetramers into variant TTR monomers, and formation of amyloid fibrils, which are consecutively deposited extracellularly in various tissues, such as nerves, heart, brain, eyes, intestines, kidneys, or the skin. Neuropathy may not only include large nerve fibers but also small fibers, and not only sensory and motor fibers but also autonomic fibers. Types of TTR variants, age at onset, penetrance, and clinical presentation vary between geographical areas. Suggestive of a ATTRm amyloidosis are a sensorimotor polyneuropathy, positive family history, autonomic dysfunction, cardiomyopathy, carpal tunnel syndrome, unexplained weight loss, and resistance to immunotherapy. If only sensory A-delta or C fibers are affected, small fiber neuropathy ensues. Diagnostic tests for small fiber neuropathy include determination of intraepidermal nerve fiber density, laser-evoked potentials, heat- and cold-detection thresholds, and measurement of the electrochemical skin conductance. Therapy currently relies on liver transplantation and TTR-stabilizers (tafamidis, diflunisal).

Neurological complications of systemic tumor therapy.

The treatment of malignant tumors has considerably improved in recent years, and also the number of "long term cancer survivors" is increasing.The spectrum of anti-tumoral agents is increasing at a fast pace and in addition to conventional therapies such as surgery, radiotherapy, and chemotherapy, new drugs with entirely new mechanisms are appearing. Side effects of old and new drugs can affect the central and peripheral nervous system, the neuromuscular junction, and muscle. These side effects often have to be distinguished from other causes and need neurological expertise. Although the majority of patients still receive conventional therapies, several new strategies such as immune therapies are being implemented. These drugs have also drug specific side effects, which do not always follow the classical principles of "toxicity."This review focuses on the well-known and described side effects of conventional cancer therapies and adds new observations on new drugs.

Chemotherapy-induced peripheral neuropathy: A current review.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect experienced by patients receiving treatment for cancer. Approximately 30 to 40% of patients treated with neurotoxic chemotherapy will develop CIPN, and there is considerable variability in its severity between patients. It is often sensory-predominant with pain and can lead to long-term morbidity in survivors. The prevalence and burden of CIPN late effects will likely increase as cancer survival rates continue to improve. In this review, we discuss the approach to peripheral neuropathy in patients with cancer and address the clinical phenotypes and pathomechanisms of specific neurotoxic chemotherapeutic agents. Ann Neurol 2017;81:772-781.

Vancouver Declaration on Global Headache Patient Advocacy 2018.

BACKGROUND: Headache disorders comprise the three most prevalent medical disorders globally and contribute almost 20% to the total burden of neurologic illness. Although the experience of a recurrent headache disorder tends to be highly individualized, patient preferences tend to be a low priority in guidelines for the management of patients with headache. METHODS: In September 2017, the first Global Patient Advocacy Summit was convened, bringing together patients, patient advocates, patient advocacy organizations, healthcare professionals, pharmaceutical manufacturers, scientists, and regulatory agencies to advance issues of importance to patients affected by headache worldwide. RESULTS: Presentations and discussion covered multiple issues, such as improving access to appropriate medical care; incorporating the insights of independent patient advocates and advocacy organizations; leveraging the insights, experience and influence of leading health and neurological organizations; and raising awareness of the role of regulatory agencies in disease advocacy. Attendees agreed that it is important to understand and promote the global, regional, and local interests of people with headache disorders, as well as challenge the pervasive stigma associated with headache. They also agreed that those with severe, recurrent, or disabling headache disorders should have reliable access to competent medical care; healthcare professionals should have access to adequate training in Headache Medicine; global benchmarks should be established for accurate diagnosis and the use of evidence-based treatments in patients with headache; and that information is needed about consultation, diagnosis, and treatment of headache, particularly in regard to patient preferences. CONCLUSION: Based on the group's consensus around these issues, a series of statements was developed, and they are collectively presented herein as the Vancouver Declaration on Global Headache Patient Advocacy 2018.

A reliable technique for ultrasound-guided perineural injection in ulnar neuropathy at the elbow.

INTRODUCTION: Ulnar neuropathy at the elbow (UNE) is a common peripheral compression neuropathy and, in most cases, occurs at 2 sites, the retroepicondylar groove or the cubital tunnel. With regard to a potential therapeutic approach with perineural corticosteroid injection, the aim of this study was to evaluate the distribution of injection fluid applied at a standard site. METHODS: We performed ultrasound-guided (US-guided) perineural injections to the ulnar nerve halfway between the olecranon and the medial epicondyle in 21 upper limbs from 11 non-embalmed cadavers. In anatomic dissection we investigated the spread of injected ink. RESULTS: Ink was successfully injected into the perineural sheath of the ulnar nerve in all 21 cases (cubital tunnel: 21 of 21; retroepicondylar groove: 19 of 21). CONCLUSION: US-guided injection between the olecranon and the medial epicondyle is a feasible and safe method to reach the most common sites of ulnar nerve entrapment. Muscle Nerve 56: 237-241, 2017.

Ultrasound and anatomical correlation of the radial nerve at the arcade of Frohse.

INTRODUCTION: In this anatomical study we evaluated the feasibility of ultrasound (US) guided perineural injection of the deep branch of the radial nerve (DBRN) at the arcade of Frohse as potential therapy for nerve entrapment at this site. METHODS: We examined 21 arms from 11 nonembalmed cadavers with US. Under US guidance, we injected ink into the DBRN perineural sheath beneath the arcade of Frohse. In subsequent anatomical dissection we evaluated the distribution of the ink. RESULTS: It was possible to apply ink at the DBRN in 95%. In 80% the ink remained within the supinator and did not reach the DBRN segment proximal to the arcade. CONCLUSIONS: With US guidance, it is possible to apply injection fluid safely around the DBRN inside the supinator tunnel. Due to the limited extent of the fluid, a second injection proximal to the arcade should be considered in the clinical setting.

Neuromuscular issues in systemic disease.

The neuromuscular system can be involved in several systemic conditions. Clinical manifestations can appear at onset or throughout the course of the disease process. New investigational methods, including imaging of peripheral nerves, new laboratory tests, and antibodies, are available. In addition to symptomatic therapies, specific treatment options, such as for familial amyloid neuropathy and Fabry's disease, are becoming increasingly available. Pathomechanisms vary depending on the underlying disease process. In addition to metabolic, hormonal, immune, and antibody-mediated mechanisms, in some generalized diseases, genetic causes need to be considered. This review focuses on different aspects of the peripheral nervous system including the nerve roots, plexuses, mononeuropathies and generalized neuropathies, neuromuscular junction disorders, muscle, and autonomic nervous system.

Longitudinal Gliding of the Median Nerve in the Carpal Tunnel: Ultrasound Cadaveric Evaluation of Conventional and Novel Concepts of Nerve Mobilization.

OBJECTIVE: To evaluate median nerve excursion during conventional nerve gliding exercises and newly developed exercises, primarily comprising abduction and adduction of the fingers. DESIGN: Descriptive study. SETTING: Anatomical dissection facility. CADAVERS: Random sample of upper extremities of fresh whole-body human cadavers (N=18). Cadavers with neuromuscular diseases in the medical record or anatomic variations were excluded. INTERVENTION: Conventional and new nerve gliding exercises. MAIN OUTCOME MEASURES: Distances between markers applied into the nerve and markers in the periosteum were visualized with ultrasound and measured. Comparisons of nerve excursions between different exercises were performed. RESULTS: Conventional exercises led to substantial nerve gliding proximal to the carpal tunnel and between the head of the pronator teres (12 and 13.8mm, respectively), but it led to far less in the carpal tunnel (6.6mm). With our novel exercises, we achieved nerve gliding in the carpal tunnel of 13.8mm. No substantial marker movement could be detected during lateral flexion of the cervical spine. CONCLUSIONS: Although conventional nerve gliding exercises only lead to minimal nerve excursions in the carpal tunnel, our novel exercises with the abduction and adduction of the fingers result in substantial longitudinal gliding throughout the arm. Clinical trials will have to deliver the clinical evidence.

Anatomical and ultrasound correlation of the superficial branch of the radial nerve.

INTRODUCTION: This anatomical study evaluates the role and correlation of ultrasound (US) with anatomy in depicting the superficial branch of the radial nerve (SBRN) and to evaluate the feasibility of US guided perineural infiltration as a potential therapeutic option in Wartenberg syndrome. METHODS: Twenty-one arms from 11 non-embalmed cadavers were examined with US. Under US guidance perineural injection with ink was performed proximal to the site where the SBRN perforates the forearm fascia. The distribution of ink around the nerve was evaluated with dissection. RESULTS: US allowed the distinction of the SBRN segments and their relation to the fascia. In all cases, the subfascial segment was stained. In only 57% the subfascially applied ink also reached the subcutaneous compartment. CONCLUSIONS: With US it is possible to examine and differentiate all segments of the SBRN. US guidance can be used for perineural injection of all relevant segments.