Handbook of clinical neurology最新文献

Peripheral nerves are functional networks in the body. Disruption of these networks induces varied functional consequences depending on the types of nerves and organs affected. Despite the advances in microsurgical repair and understanding of nerve regeneration biology, restoring full functions after severe traumatic nerve injuries is still far from achieved. While a blunted growth response from axons and errors in axon guidance due to physical barriers may surface as the major hurdles in repairing nerves, critical additional cellular and molecular aspects challenge the orderly healing of injured nerves. Understanding the systematic reprogramming of injured nerves at the cellular and molecular levels, referred to here as "hallmarks of nerve injury regeneration," will offer better ideas. This chapter discusses the hallmarks of nerve injury and regeneration and critical points of failures in the natural healing process. Potential pharmacological and nonpharmacological intervention points for repairing nerves are also discussed.

Autologous hematopoietic stem cell transplantation (HSCT) is associated with 5-year treatment-free remissions in approximately 80% of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who failed or were dependent on intravenous immunoglobulin and or plasmapheresis. Autologous HSCT was associated with significant improvement in strength, independent ambulation, quality of life, nerve conduction velocity, and compound muscle action potential amplitude. The results of HSCT are dependent on proper patient selection, i.e., the right diagnosis and the right stage of the disease. An important caveat is that a significant number of patients with a CIDP diagnostic label are found upon further workup have a peripheral neuropathy of another etiology. Patients undergoing HSCT for CIDP should be reevaluated before HSCT to confirm the diagnosis and those who fail HSCT should be reevaluated for a diagnosis other than CIDP.

Recent advances in neuroimmunology have shed light on the pathogenic mechanisms underlying rare neuroimmunologic conditions such as myasthenia gravis (MG) and stiff person syndrome (SPS). Despite the rarity of these conditions, their complex manifestations and potential for irreversible disability necessitate effective therapeutic strategies. This chapter reviews the current understanding of the safety and efficacy of hematopoietic stem cell transplantation (HSCT) in MG and SPS. Several case reports and retrospective studies have demonstrated promising outcomes following HSCT in refractory MG and SPS, with significant clinical improvement and even discontinuation of chronic immunomodulatory therapy in some cases. Furthermore, HSCT may offer insights into the underlying pathophysiologic mechanisms of these conditions, particularly the role of cellular immunity. Although more research is needed to fully understand the impact of HSCT on disease pathology and outcomes, current evidence suggests that HSCT could be a valuable therapeutic option for patients with refractory MG and SPS.

Migraine is a prevalent and disabling neurological disease. Its preventive treatment for decades has been rather limited due to the absence of disease-specific therapies with limited efficacy and tolerability. The advances made in migraine research have led to the discovery of the calcitonin gene-related peptide (CGRP) and its role in migraine pathophysiology. CGRP is a neuropeptide that acts as potent vasodilator and is involved in pain processing. Increased levels of plasma CGRP have been observed during migraine attacks as well as interictally when comparing patients with migraine and healthy controls. In the last years, two classes of drugs antagonizing CGRP have therefore been developed as the first migraine-specific preventive treatments: anti-CGRP monoclonal antibodies (mAbs) and gepants. Four mAbs have been approved: erenumab, galcanezumab, fremanezumab, and eptinezumab. Gepants are small molecules that antagonize the CGRP receptor; currently only rimegepant and atogepant have been approved for migraine prevention. These new drugs have demonstrated efficacy and safety in clinical trials for both episodic and chronic migraine, and results from their real-world experience are being increasingly reported in literature. In this review, we provide an overview of anti-CGRP drugs and their placement in migraine prevention.

Migraine is a complex, multifactorial brain disorder, and its presentation, complications, and response to treatment often follow the biopsychosocial model. Therefore, assessment and management include the wider aspects of the child's life within the family, at school, with peers, and in relation to his/her neurologic and emotional development. The diagnosis of headache disorders in children relies heavily on taking a careful clinical history, carrying out an appropriate physical and neurologic examination and a skilled interpretation of the findings. This chapter discusses the peculiarities of migraine in children, the differences in presentation from that in adults, and the skills that are needed in assessing the children and adolescents with headache. There is also a brief review of the epidemiology of headache and migraine in children and adolescents and an introduction of the principles of a comprehensive clinical assessment of the impact of migraine on child's quality of life. Several important elements of the clinical history and the physical and neurologic examination will be illustrated to help in the early detection of red flags that may necessitate further assessment and/or investigations. At the end of the assessment, the clinicians will be able to employ the International Classification of headache Disorders and make the correct diagnosis.

As a common headache disorder, migraine is also a common cause for emergency department (ED) visiting, which leads to tremendous medical and economic burden. The goals of migraine management in ED are resolving headache and migraine-related most bothersome symptoms rapidly, preventing ED revisiting due to headache relapse, and referring patients at risk, e.g., patients with chronic migraine and/or medication-overuse headache, to specialists. In this chapter, we elucidated the algorithm which was particularly adapted to ED settings for the diagnosis and treatment of migraine. We reviewed a plentiful amount of high-quality clinical trials, especially those conducted in populations derived from ED, to provide readers insights into the optimized treatment options for migraine in ED.

Andersen-Tawil syndrome (ATS) is one of the periodic paralyses, a set of skeletal muscle disorders that cause transient weakness of the arms and legs lasting minutes to many hours. Distinguishing features of ATS include facial and limb dysmorphisms, cardiac arrhythmia, difficulties with executive function, and association with dominant mutations in the potassium channel, KCNJ2. In this review, we discuss the key features of ATS, diagnostic testing, pathophysiology and treatment of ATS, and compare them with other periodic paralyses.

Paroxysmal movement disorders include two groups of intermittent neurologic disorders: paroxysmal dyskinesia, in which episodes of involuntary hyperkinetic movements (mainly chorea and/or dystonia) occur with preserved consciousness, and episodic ataxias, which are characterized by discrete attacks of cerebellar dysfunction, sometimes associated with progressive ataxia. Since episodic ataxias are individually discussed in Chapter 8 of this volume, we herein provide a deep overview of phenotypic, genetic, pathophysiologic, diagnostic, and treatment aspects of paroxysmal dyskinesia, following the trigger-based nomenclature which distinguishes paroxysmal kinesigenic dyskinesia, paroxysmal nonkinesigenic dyskinesia, and paroxysmal exercise-induced dyskinesia. Emerging paroxysmal dyskinesia not fulfilling the criteria for the above-mentioned subtypes will also be discussed. Phenotypic and genotypic overlap among paroxysmal movement disorders, epilepsy, and migraine have progressively emerged, thus shedding light on a shared pathophysiologic framework. Advances in our understanding of the pathomechanisms underlying paroxysmal movement disorders, which involve dysfunctions of ion channels, proteins associated with the vesical synaptic cycle machinery, and proteins involved in neuronal energy metabolism, point toward a discrete number of converging pathophysiologic pathways and may lay foundations for developing target-specific therapies.

Neuromyotonia is continuous peripheral nerve hyper-excitability manifesting in muscle twitching at rest (myokymia), inducible cramps and impaired muscle relaxation, and characterized by EMG findings of spontaneous single motor unit discharges (with doublet, triplet, or multiplet morphology). The disorder may be genetic, acquired, and often in the acquired cases autoimmune. This chapter focuses on autoimmune acquired causes. Autoimmune associations include mainly contactin-associated protein-like 2 (CASPR2) antibody-associated disease (previously termed as VGKC or voltage-gated potassium channel antibody-associated neuromyotonia) (van Sonderen et al., 2016, p. 2), leucine-rich glioma-inactivated 1 (LGI1) antibody disease, the Guillain-Barré syndrome, NMDAR encephalitis (Varley et al., 2019), and IgLON5 (Gaig et al., 2021) disease. Nonimmune associations include radiation-induced plexopathy. An association with myasthenia gravis and other autoimmune disorders, response to plasma exchange (Newsom-Davis and Mills, 1993) and physiologically induced changes in mice injected with patient-derived immunoglobulins led to the discovery of autoantibodies to juxtaparanodal proteins complexed with potassium channels (Shillito et al., 1995). The target of the antibodies is most commonly the CASPR2 protein. The disorder may be paraneoplastic, and a search for and treatment of an underlying tumor is a necessary step. In cases in which there is evidence for an immune cause, then immune suppression, with an emerging role for B cell-depleting therapies, is associated with a good clinical outcome. In parallel, sodium channel blocking drugs remain effective symptomatic therapies.

Autologous hematopoietic stem cell transplantation (aHSCT) may be effective in carefully selected pediatric patients with multiple sclerosis (MS), neuromyelitis optica (NMO), and chronic inflammatory demyelinating polyneuropathy (CIDP). aHSCT for pediatric MS (same as for adults) is performed to eradicate inflammatory autoreactive cells with lympho-ablative regimens and restore immune tolerance. Its therapeutic effect in MS relies on various mechanisms: (1) the immunosuppressive conditioning regimen prior to aHSCT was able to eradicate the autoreactive cells and (2) the regeneration/renewal of the immune system to reset the aberrant immune response against self-antigens. The aHSCT procedure includes the following different steps, as described in this chapter: patient selection through careful pretransplant screening, "wash-out" period from previous treatments, mobilization of hematopoietic stem cells (HSC), conditioning regimen, HSC infusion, and posttransplant monitoring for early and late complications. Moreover, specific aspects of pediatric population undergoing aHSCT are described. According to the available evidence, aHSCT appears to be safe in pediatric MS, obtaining disease control for a prolonged time after the procedure. A reasonable approach in this setting includes the application of less toxic treatments while reserving aHSCT procedure for patients with severe/refractory forms of the disease. The EBMT considers MS, NMO, and CIDP in pediatric patients within the category of the clinical option (CO), where candidates for aHSCT can be selected on the basis of careful consideration of individual case history in the multidisciplinary setting.