Occipital nerve stimulation: technical and surgical aspects of implantation

The objective of this article is to review the surgical aspects of occipital stimulation. Since 1999 there has been a growing interest in neuromodulation of the distal branches of C2-3 in an effort to treat refractory headache disorders. This is accomplished via implantation of subcutaneous electrodes to stimulate peripheral nerves in the occipital region. "Occipital nerve stimulation" is a term generically used to describe the technique. Mechanisms and outcome of this modality are beyond the scope of this review, which will focus on the technical aspects of the procedure with its associated complications such as lead migration, localized pain, and infection. The history of peripheral nerve and spinal cord stimulation as pain treatment modalities will be briefly reviewed. The equipment and surgical technique for both trial and permanent implantation of occipital nerve stimulators will be described, in addition to patient selection considerations. The available literature will be summarized and a discussion of future directions will be provided. Occipital nerve stimulation may be an effective minimally invasive treatment modality for refractory headache disorders; clearly, further studies are needed.     

The double crush syndrome revisited--a Delphi study to reveal current expert views on mechanisms underlying dual nerve disorders

A high prevalence of dual nerve disorders is frequently reported. How a secondary nerve disorder may develop following a primary nerve disorder remains largely unknown. Although still frequently cited, most explanatory theories were formulated many years ago. Considering recent advances in neuroscience, it is uncertain whether these theories still reflect current expert opinion. A Delphi study was conducted to update views on potential mechanisms underlying dual nerve disorders. In three rounds, seventeen international experts in the field of peripheral nerve disorders were asked to list possible mechanisms and rate their plausibility. Mechanisms with a median plausibility rating of ≥7 out of 10 were considered highly plausible. The experts identified fourteen mechanisms associated with a first nerve disorder that may predispose to the development of another nerve disorder. Of these fourteen mechanisms, nine have not previously been linked to double crush. Four mechanisms were considered highly plausible (impaired axonal transport, ion channel up or downregulation, inflammation in the dorsal root ganglia and neuroma-in-continuity). Eight additional mechanisms were listed which are not triggered by a primary nerve disorder, but may render the nervous system more vulnerable to multiple nerve disorders, such as systemic diseases and neurotoxic medication. Even though many mechanisms were classified as plausible or highly plausible, overall plausibility ratings varied widely. Experts indicated that a wide range of mechanisms has to be considered to better understand dual nerve disorders. Previously listed theories cannot be discarded, but may be insufficient to explain the high prevalence of dual nerve disorders.     

Les maladies neuromusculaires : diagnostic et suivi à l’âge adulte

Neuromuscular disorders are a heterogeneous group of acquired or inherited diseases involving the peripheral nerve, the muscle or the neuromuscular junction. These disorders include a wide spectrum of diagnostic difficulties, clinical severities and outcomes. This review will focus on modalities and pitfalls of the diagnostic process. It will also describe the hallmarks of the follow-up in adulthood.     

Role of skin biopsy in the diagnosis of peripheral neuropathic pain

Evaluation of epidermal nerve fiber density (ENFD) allows objective, pathologic, and minimally invasive assessment of small myelinated and unmyelinated cutaneous axons. In addition to providing diagnostic confirmation of neuropathies affecting these “small fibers,” this procedure has advanced clinical care by dramatically increasing awareness of the role of small myelinated and unmyelinated axons in disorders of peripheral nerve and in neuropathic pain. This review highlights the technical aspects of skin biopsy for ENFD determination, the role of skin biopsy in the diagnosis of small-fiber neuropathy and ganglionopathy, and the diagnostic approach to the patient with peripheral neuropathic pain.     

Peripheral Nerve Blocks and Trigger Point Injections in Headache Management – A Systematic Review and Suggestions for Future Research

(Headache 2010;50:943‐952) Interventional procedures such as peripheral nerve blocks (PNBs) and trigger point injections (TPIs) have long been used in the treatment of various headache disorders. There are, however, little data on their efficacy for the treatment of specific headache syndromes. Moreover, there is no widely accepted agreement among headache specialists as to the optimal technique of injection, type, and doses of the local anesthetics used, and injection regimens. The role of corticosteroids in this setting is also debated. We performed a PubMed search of the literature to find studies on PNBs and TPIs for headache treatment. We classified the abstracted studies based on the procedure performed and the treated condition. We found few controlled studies on the efficacy of PNBs for headaches, and virtually none on the use of TPIs for this indication. The most widely examined procedure in this setting was greater occipital nerve block, with the majority of studies being small and non‐controlled. The techniques, as well as the type and doses of local anesthetics used for nerve blockade, varied greatly among studies. The specific conditions treated also varied, and included both primary (eg, migraine, cluster headache) and secondary (eg, cervicogenic, posttraumatic) headache disorders. Trigeminal (eg, supraorbital) nerve blocks were used in few studies. Results were generally positive, but should be taken with reservation given the methodological limitations of the available studies. The procedures were generally well tolerated. Evidently, there is a need to perform more rigorous clinical trials to clarify the role of PNBs and TPIs in the management of various headache disorders, and to aim at standardizing the techniques used for the various procedures in this setting.     

Structural and functional assessment of skin nerve fibres in small‐fibre pathology

Damage to nociceptor nerve fibres may give rise to peripheral neuropathies, some of which are pain free and some are painful. A hallmark of many peripheral neuropathies is the loss of small nerve fibres in the epidermis, a condition called small‐fibre neuropathy (SFN) when it is predominantly the small nerve fibres that are damaged. Historically, SFN has been very difficult to diagnose as clinical examination and nerve conduction studies mainly detect large nerve fibres, and quantitative sensory testing is not sensitive enough to detect small changes in small nerve fibres. However, taking a 3‐mm punch skin biopsy from the distal leg and quantification of the nerve fibre density has proven to be a useful method to diagnose SFN. However, the correlation between the nerve fibre loss and other test results varies greatly. Recent studies have shown that it is possible not only to extract information about the nerve fibre density from the biopsies but also to get an estimation of the nerve fibre length density using stereology, quantify sweat gland innervation and detect morphological changes such as axonal swelling, all of which may be additional parameters indicating diseased small fibres relating to symptoms reported by the patients. In this review, we focus on available tests to assess structure and function of the small nerve fibres, and summarize recent advances that have provided new possibilities to more specifically relate structural findings with symptoms and function in patients with SFN.     

Sonography of Common Peripheral Nerve Disorders With Clinical Correlation

Sonography is now considered an effective method to evaluate peripheral nerves. Low cost, high resolution, the ability to image an entire limb in a short time, and dynamic assessment are several of the positive attributes of sonography. This article will review the normal appearance of peripheral nerves as shown with sonography. In addition, the most common applications for sonography of the peripheral nerves will be reviewed, which include entrapment neuropathies, intraneural ganglion cyst, nerve trauma, and peripheral nerve sheath tumors. Clinical information related to nerve disorders is also included, as it provides valuable information that can be obtained during sonographic examinations, increasing diagnostic accuracy.     

Value of imaging in disorders of the facial nerve

Imaging of the facial nerve has proved its usefulness to physicians in the evaluation of pathological conditions of this nerve. Magnetic resonance imaging (MRI) of the facial nerve should always be obtained selectively and should include the parotid gland in case of peripheral facial nerve palsy. Gadolinium-DTPA contrast pulse sequence is the most informative MRI study for evaluation of facial nerve pathology. This article reviews the imaging anatomy of the facial nerve and describes the clinical features and MR characteristics of common disorders of the facial nerve.     

Musculoskeletal complications of neuromuscular disease in children

A wide variety of neuromuscular diseases affect children, including central nervous system disorders such as cerebral palsy and spinal cord injury; motor neuron disorders such as spinal muscular atrophy; peripheral nerve disorders such as Charcot-Marie-Tooth disease; neuromuscular junction disorders such as congenital myasthenia gravis; and muscle fiber disorders such as Duchenne's muscular dystrophy. Although the origins and clinical syndromes vary significantly, outcomes related to musculoskeletal complications are often shared. The most frequently encountered musculoskeletal complications of neuromuscular disorders in children are scoliosis, bony rotational deformities, and hip dysplasia. Management is often challenging to those who work with children who have neuromuscular disorders.     

Neurotoxins in the Neurobiology of Pain

Migraine is a common, chronic, incapacitating, neurovascular disorder that affects an estimated 12% of the population. Understanding the basic mechanisms of pain is important when treating patients with chronic pain disorders.
Pain, an unpleasant sensory and emotional experience, is usually triggered by stimulation of peripheral nerves and often associated with actual or potential tissue damage. Peripheral nerve fibers transmit pain signals from the periphery toward the spinal cord or brain stem. The different diameter pain fibers (A and C) vary in the speed of conduction and the type of pain transmitted (eg, sharp versus dull). When stimulated, peripheral pain fibers carrying sensory input from the body enter at different layers of the dorsal horn, which is then propagated toward the thalamus via the spinothalamic tract within the spinal cord. Conversely, sensory input from the face does not enter the spinal cord but enters the brain stem via the trigeminal nerve.
This review describes in detail the neurobiological mechanisms and pathways for pain sensation, with a focus on migraine pain.     

Spared nerve injury: an animal model of persistent peripheral neuropathic pain

Peripheral neuropathic pain is produced by multiple etiological factors that initiate a number of diverse mechanisms operating at different sites and at different times and expressed both within, and across different disease states. Unraveling the mechanisms involved requires laboratory animal models that replicate as far as possible, the different pathophysiological changes present in patients. It is unlikely that a single animal model will include the full range of neuropathic pain mechanisms. A feature of several animal models of peripheral neuropathic pain is partial denervation. In the most frequently used models a mixture of intact and injured fibers is created by loose ligation of either the whole (Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988;33:87-107) or a tight ligation of a part (Seltzer Z, Dubner R, Shir Y. A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 1990;43:205-218) of a large peripheral nerve, or a tight ligation of an entire spinal segmental nerve (Kim SH, Chung JM. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 1992;50:355-363). We have developed a variant of partial denervation, the spared nerve injury model. This involves a lesion of two of the three terminal branches of the sciatic nerve (tibial and common peroneal nerves) leaving the remaining sural nerve intact. The spared nerve injury model differs from the Chung spinal segmental nerve, the Bennett chronic constriction injury and the Seltzer partial sciatic nerve injury models in that the co-mingling of distal intact axons with degenerating axons is restricted, and it permits behavioral testing of the non-injured skin territories adjacent to the denervated areas. The spared nerve injury model results in early (<24 h), prolonged (>6 months), robust (all animals are responders) behavioral modifications. The mechanical (von Frey and pinprick) sensitivity and thermal (hot and cold) responsiveness is increased in the ipsilateral sural and to a lesser extent saphenous territories, without any change in heat thermal thresholds. Crush injury of the tibial and common peroneal nerves produce similar early changes, which return, however to baseline at 7-9 weeks. The spared nerve injury model may provide, therefore, an additional resource for unraveling the mechanisms responsible for the production of neuropathic pain.     

Schmerzsyndrome des Bewegungsapparates

Clinical pain syndromes affecting the locomotor apparatus can become apparent not only in the form of nociceptive pain in the skeleto-mechanical system, but also as neurogenic pain emanating from lesions in the peripheral nerves or nerve roots or as referred pain resulting from disorders of visceral organs. The anatomical structure and basic innervation can contribute to the various characteristics of such deep pain. Within the spinal cord, visceral and somatic afferent fibres converge on nociceptive pathways, resulting in a uniform clinical pain syndrome. The differential diagnosis can be extremely difficult when attempts are made to evaluate its clinical relevance. Pain radiating from deep somatic tissues into the extremities is called "pseudoradicular" pain. Examples are encountered in the "facet syndrome" or the "myofascial pain syndrome". Various types of treatment are available for musculo-skeletal disorders, including physiotherapy, transcutaneous nerve stimulation (TENS) and trigger point infiltration. In clinical practice, however, drug therapy with peripheral analgesics and anti-inflammatory drugs is the form of therapy most often prescribed. There is no doubt that these drugs can help a great deal. However, they have only a symptomatic effect without any influence on the origin or course of the disease. Therefore, a critical evaluation of their benefits and risks is required before treatment with such drugs is instituted.     

Novel and Emerging Electrophysiological Biomarkers of Diabetic Neuropathy and Painful Diabetic Neuropathy

PurposeDiabetic peripheral neuropathy (DPN) is the most common complication of diabetes. Small and large peripheral nerve fibers can be involved in DPN. Large nerve fiber damage causes paresthesia, sensory loss, and muscle weakness, and small nerve fiber damage is associated with pain, anesthesia, foot ulcer, and autonomic symptoms. Treatments for DPN and painful DPN (pDPN) pose considerable challenges due to the lack of effective therapies. To meet these challenges, there is a major need to develop biomarkers that can reliably diagnose and monitor progression of nerve damage and, for pDPN, facilitate personalized treatment based on underlying pain mechanisms.MethodsThis study involved a comprehensive literature review, incorporating article searches in electronic databases (Google Scholar, PubMed, and OVID) and reference lists of relevant articles with the authors’ substantial expertise in DPN. This review considered seminal and novel research and summarizes emerging biomarkers of DPN and pDPN that are based on neurophysiological methods.FindingsFrom the evidence gathered from 145 papers, this submission describes emerging clinical neurophysiological methods with potential to act as biomarkers for the diagnosis and monitoring of DPN as well as putative future roles as predictors of response to antineuropathic pain medication in pDPN. Nerve conduction studies only detect large fiber damage and do not capture pathology or dysfunction of small fibers. Because small nerve fiber damage is prominent in DPN, additional biomarkers of small nerve fiber function are needed. Activation of peripheral nociceptor fibers using laser, heat, or targeted electrical stimuli can generate pain-related evoked potentials, which are an objective neurophysiological measure of damage along the small fiber pathways. Assessment of nerve excitability, which provides a surrogate of axonal properties, may detect alterations in function before abnormalities are detected by nerve conduction studies. Microneurography and rate-dependent depression of the Hoffmann-reflex can be used to dissect underlying pain-generating mechanisms arising from the periphery and spinal cord, respectively. Their role in informing mechanistic-based treatment of pDPN as well as facilitating clinical trials design is discussed.ImplicationsThe neurophysiological methods discussed, although currently not practical for use in busy outpatient settings, detect small fiber and early large fiber damage in DPN as well as disclosing dominant pain mechanisms in pDPN. They are suited as diagnostic and predictive biomarkers as well as end points in mechanistic clinical trials of DPN and pDPN.     

Genetics of neuromuscular disorders

Neuromuscular disorders affect the peripheral nervous system and muscle. The principle effect of neuromuscular disorders is therefore on the ability to perform voluntary movements. Neuromuscular disorders cause significant incapacity, including, at the most extreme, almost complete paralysis. Neuromuscular diseases include some of the most devastating disorders that afflict mankind, for example motor neuron disease. Neuromuscular diseases have onset any time from in utero until old age. They are most often genetic. The last 25 years has been the golden age of genetics, with the disease genes responsible for many genetic neuromuscular disorders now identified. Neuromuscular disorders may be inherited as autosomal dominant, autosomal recessive, or X-linked traits. They may also result from mutations in mitochondrial DNA or from de novo mutations not present in the peripheral blood DNA of either parent. The high incidence of de novo mutation has been one of the surprises of the recent increase in information about the genetics of neuromuscular disorders. The disease burden imposed on families is enormous including decision making in relation to presymptomatic diagnosis for late onset neurodegenerative disorders and reproductive choices. Diagnostic molecular neurogenetics laboratories have been faced with an ever-increasing range of disease genes that could be tested for and usually a finite budget with which to perform the possible testing. Neurogenetics has moved from one known disease gene, the Duchenne muscular dystrophy gene in July 1987, to hundreds of disease genes in 2011. It can be anticipated that with the advent of next generation sequencing (NGS), most, if not all, causative genes will be identified in the next few years. Any type of mutation possible in human DNA has been shown to cause genetic neuromuscular disorders, including point mutations, small insertions and deletions, large deletions and duplications, repeat expansions or contraction and somatic mosaicism. The diagnostic laboratory therefore has to be capable of a large number of techniques in order to identify the different mutation types and requires highly skilled staff. Mutations causing neuromuscular disorders affect the largest human proteins for example titin and nebulin. Successful molecular diagnosis can make invasive and expensive diagnostic procedures such as muscle biopsy unnecessary. Molecular diagnosis is currently largely based on Sanger sequencing, which at most can sequence a small number of exons in one gene at a time. NGS techniques will facilitate molecular diagnostics, but not for all types of mutations. For example, NGS is not good at identifying repeat expansions or copy number variations. Currently, diagnostic molecular neurogenetics is focused on identifying the causative mutation(s) in a patient. In the future, the focus might move to prevention, by identifying carriers of recessive diseases before they have affected children. The pathobiology of many of the diseases remains obscure, as do factors affecting disease severity. The aim of this review is to describe molecular diagnosis of genetic neuromuscular disorders in the past, the present and speculate on the future.     

周围神经损伤后修复再生的研究进展

周围神经损伤是手显微外科的常见病,其治疗及功能恢复一直都是手显微外科的难题。周围神经缺损后如何促进再生修复,提高神经缺损的治疗效果,使患者功能恢复较好,一直是临床研究的重点、热点、难点。近年来随着基础研究的不断深入,人们对周围神经解剖及其再生微环境的认识,周围神经损伤治疗方法已经由药物治疗、手术治疗发展到基因工程等,为周围神经损伤患者的治疗提供了更好的治疗思路。本文就周围神经缺损后周围神经修复的方法作一综述。     

Bilateral dorsal foot pain in a young tennis player managed by neurodynamic treatment techniques

Exercise-related lower limb pain represents one of the most common presentations in sports medicine practice. This is usually caused by musculoskeletal overuse injuries but not uncommonly, a neuropathic cause may be suspected. A review of the literature revealed that peripheral neuropathic pain has never been documented in a child. It is possible that peripheral neuropathic pain of spinal origin may be more prevalent in children than previously recognized. This case report describes the presentation of a 12 year old tennis player with bilateral dorsal foot pain, who presented with positive findings of peripheral nerve sensitization which was successfully managed using neurodynamic treatment techniques. Differential diagnoses are considered and treatment and management described. A discussion of the clinical reasoning which led to the patient’s diagnosis is included. This case report suggests the effectiveness of neurodynamic treatment in a child with bilateral foot pain who fulfilled published criteria for peripheral nerve sensitization. However, the single case methodology employed in this study limits generalization of its findings. Further studies are warranted to investigate the role of neurodynamics in musculoskeletal pain disorders in children.     

基于角膜共聚焦显微镜的神经纤维人工智能分析方法

糖尿病周围神经病变(diabetic peripheral neuropathy, DPN)是糖尿病最常见的慢性并发症之一。基于临床症状体征以及电生理检查的传统DPN诊断方法主要用于检测大神经纤维病变,而DPN最早出现损伤的部位是小神经纤维。角膜共聚焦显微镜(corneal confocal microscopy, CCM)能够在高倍镜下分析角膜神经纤维的变化,是一种快速、可重复、定量测量小神经纤维病变的无创技术,可早期诊断DPN并前瞻性评估神经形态学改变,具有良好的应用前景。本文就CCM评估糖尿病神经病变的临床应用研究以及CCM相关人工智能分析方法进行综述,以期为临床诊疗提供借鉴。     

Single fiber electromyography with a standard monopolar electrode

A technique of obtaining qualitative single fiber electromyography information with standard monopolar electrodes is described. The technique requires an electromyograph equipped with a trigger and delay line. Single fiber electromyography is an effective tool in dealing with disorders that affect neuromuscular transmission and for observing the recovery of nerve injuries. Since most problems encountered in clinical practice deal with the diagnosis and follow-up of radiculopathies and peripheral nerve compromise, the use of single fiber electromyography in these conditions is of great clinical importance.     

Sonographic Evaluation of Common Peroneal Neuropathy in Patients With Foot Drop

The common peroneal nerve arises from the sciatic nerve and is subject to a variety of abnormalities. Although diagnosis is often is based on the clinical findings and electrodiagnostic tests, high‐resolution sonography has an increasing role in determining the type and location of common peroneal nerve abnormalities and other peripheral nerve disorders. This article reviews the normal sonographic appearance of the common peroneal nerve and the findings in 21 patients with foot drop related to common peroneal neuropathy.     

Uremic neuropathy. III. Controlled study of restricted protein and fluid diet and infrequent hemodialysis versus conventional hemodialysis treatment.

The effect of a treatment schedule of restricted protein and fluid intake and of infrequent hemodialysis (schedule 1) as compared to a conventional hemodialysis treatment schedule (schedule 2) on the presence and severity of peripheral neuropathy has been studied in a small group of patients using a crossover design. Using the neurologic evaluation and quantitative assessment of cutaneous sensation and of nerve conduction as indices of peripheral nerve function, we have not demonstrated any worsening of peripheral nerve function from markedly curtailing the frequency of hemodialysis and modifying the diet. Because of the small size of the study, the preponderance of patients receiving the test treatment schedule first, and the possibility that nerve function slowly worsens with time, it is not possible to say with certainty that the test or the control treatment schedule might adversely affect peripheral nerve function. If such an effect is present it would appear to be small.