Handbook of clinical neurology最新文献

Pharmacotherapies are the mainstays of migraine management, though it is not uncommon for them to be poorly tolerated, contraindicated, or only modestly effective. There is a clear need for nonpharmacologic migraine therapies, either employed alone or in combination with pharmacotherapies. Behavioral and psychosocial factors known to contribute to the onset, exacerbation, and persistence of primary headache disorders (e.g., stress, sleep, diet) serve as targets within a self-management model for migraine-a model that features headache pharmacotherapies, behavioral skills training, medication adherence facilitation, relevant lifestyle changes, and techniques to limit headache-related impairment. Behavioral self-management interventions for migraine with the strongest empirical validation (e.g., relaxation training, biofeedback training, cognitive-behavior therapies) presently are available in specialty headache treatment centers and routinely show promise for reducing headache pain frequency/severity and related impairment, reducing reliance on pharmacotherapies, enhancing personal control over headache activity, and reducing headache-related distress and symptoms. These approaches may be particularly well-suited among patients for whom pharmacotherapies are unwanted, poorly tolerated, or contraindicated. Though underutilized, clinical trials indicate that new and well-established behavioral therapies are similarly effective to migraine medications for migraine prevention among adults and can be successfully employed in various settings.

Sleep disorders are commonly found as comorbid problems in patients with migraine. Indeed, there are likely to be numerous levels of interaction between migraine and sleep, including physiological, pathological, and pharmacological. Of note, the presence of sleep disorders may be a modifiable factor in the trajectory of migraine, and therefore active enquiry to elicit their presence, and manage them appropriately, could be an important component in the holistic care of patients with migraine. This review attempts to provide an outline of what is known about these relationships and highlight where relevant which facets could be exploited for therapeutic gain.

Successful management of migraine in childhood and adolescence starts with making the correct diagnosis, assessing the impact of migraine on the child/adolescent's quality of life including impact on education, family life, and social activities. Understanding the child's and family's concerns and reasons for seeking medical advice is an important starting point in the management plan. Pharmacological treatment should go hand-in-hand with appropriate advice on maintaining a healthy life style, avoidance of triggers and aggravating factors, and exploring comorbid disorders that may influence response to treatment. Compared to those available for adult patients, pharmacologic treatment options for migraine in children and adolescents are relatively untested and limited at the present time. Therefore, an individual management plan on the appropriate use of medications, including the limitations of acute treatment and prevention of migraine, should be agreed and well understood by the patient, his/her carers, and school teachers, in order to achieve best results. Treatment of acute migraine episodes should be given as early as possible after onset of headache using an appropriate dose to child's age and weight and in the correct formulation and route of administration. Preventive treatment should be given regularly in a dose titrated to achieve maximum benefit with least adverse effect for at least 6-8 weeks before a judgment is made on its efficacy. Regular monitoring of treatment response can be facilitated by prospective headache diaries and follow-up.

Migrainous infarction is defined as a migraine attack occurring as migraine with aura, typical of the patient's previous attacks, except that one or more aura symptoms persist for >60min, and neuroimaging demonstrates ischemic infarct in the relevant area. To better understand migrainous infarction, one must disentangle the complex interactions between migraine and stroke. In this chapter, we first discuss the migraine-stroke association in sections including "Increased Risks of Stroke and Subclinical Infarcts in Patients With Migraine," "Migrainous Headache Cooccurring or Triggered by Ischemic Stroke," "Stroke Progression in Patients With Migraine," and "Clinic Conditions Associated With Higher Risks of Both Migraine and Stroke." As an extreme example of migraine-stroke association, the annual incidence of migrainous infarction was reported to be 0.80/100,000/year, with the incidence in females nearly twofold that of male patients. Patients diagnosed with migrainous infarction are typically younger (average age 29-39 in case series), have fewer traditional vascular risk factors, and have more favorable prognosis compared to strokes from traditional risk factors. Thorough evaluation is recommended to rule out other etiologies of stroke. Patients diagnosed with migrainous infarction should receive antiplatelet therapy and migraine preventive therapy to avoid future events. Vasoactive medications, including triptans and ergots, should be avoided.

The acute treatment of migraine attacks should provide rapid, effective, and long-lasting symptom relief, causing minimal adverse effects. For this purpose, there are several specific and nonspecific acute treatments. In this chapter, we focus on molecules not specifically designed for migraines, including anti-inflammatory not specific analgesics, such as acetaminophen, acetylsalicylic acid, and other non-steroidal anti-inflammatory drugs (or COX-2 inhibitors); antinausea medications like metoclopramide or prochlorperazine, which can alleviate sickness and vomiting associated with migraines, and may also have a direct painkiller effect; combinations of simple analgesics or association of a painkiller with caffeine. This stimulant can help enhance the pain-relieving effects of some headache medications and provide its own analgesic effect; physical approaches: applying cold packs or heating pads on the forehead or neck, can help relieve migraine pain; other classes with limited to no evidence to support their use, such as intravenous corticosteroids or antiepileptic drugs as sodium valproate. Finally, we will briefly mention opioids, barbiturates, or medical cannabis, bearing in mind that their use is not recommended by current guidelines.

The advent of the triptans revolutionized acute migraine treatment. The older migraine-specific drugs, the ergot alkaloids (ergotamine and dihydroergotamine), also relieve migraine attacks through agonism at the 5-HT_1B and 5-HT_1D receptors, but the triptans have much greater specificity for these receptors. Unlike the ergot alkaloids, the triptans do not activate many other receptor types, and therefore are much better tolerated. This reduction in side effects greatly enhanced their clinical utility as it allowed a far greater proportion of patients to take a full therapeutic dose. As a result, the clinical use of ergotamine is minimal today, although dihydroergotamine still has a significant clinical role. There is extensive evidence that the seven triptans available today, sumatriptan, zolmitriptan, rizatriptan, eletriptan, naratriptan, almotriptan, and frovatriptan, are effective in the acute treatment of migraine. Available formulations include oral tablets, orally dissolving tablets, subcutaneous injections, nasal sprays, and in some countries, rectal suppositories. For optimal benefit, therapy needs to be individualized for a given patient both regarding the triptan chosen and the formulation. This chapter discusses the ergot alkaloids and the triptans, including mechanism of action, evidence for efficacy, clinical use, and adverse effects.

Piriformis syndrome is a condition that is proposed to result from compression of the sciatic nerve, either in whole or in part, in the deep gluteal space by the piriformis muscle. The prevalence of piriformis syndrome depends upon the diagnostic criteria being used and the population studied but is estimated by some to be 5%-6% in all cases of low back, buttock, and leg pain and up to 17% of patients with chronic low back pain. While the sciatic nerve may pierce the piriformis muscle in about 16% of healthy individuals, this frequency is no different in those with the syndrome; thus, the relationship to this anatomic finding is unclear. The most common symptoms are buttock pain, external tenderness over the greater sciatic notch, and aggravation of the pain through sitting. Many clinical signs are reported for piriformis syndrome, but the sensitivity and specificity are unclear, in part because of the lack of a uniformly accepted case definition. In the majority of cases in the literature, it appears that the diagnosis is more ascribed to a myofascial condition rather than a focal neuropathy. Electrodiagnostic studies can be useful to exclude other causes of symptoms, but there is no well-accepted test to confirm the presence of piriformis syndrome. Ultrasound imaging may show thickening of the piriformis muscle, but further research is required to confirm that this is correlated with the clinical diagnosis. Magnetic resonance imaging and neurography may hold promise in the future, but there are not yet sufficient data to support adopting these methods as a standard diagnostic tool. The initial treatment of piriformis syndrome is typically conservative management with the general rehabilitation principles similar to other soft tissue musculoskeletal conditions. Local anesthetic, botulinum toxin, and/or corticosteroid injections have been reported by some to be beneficial for diagnostic or treatment purposes. Surgical interventions have also been used with variable success.

Radial neuropathy is the third most common upper limb mononeuropathy after median and ulnar neuropathies. Muscle weakness, particularly wrist drop, is the main clinical feature of most cases of radial neuropathy, and an understanding of the radial nerve's anatomy generally makes localizing the lesion straightforward. Electrodiagnosis can help confirm a diagnosis of radial neuropathy and may help with more precise localization of the lesion. Nerve imaging with ultrasound or magnetic resonance neurography is increasingly used in diagnosis and is important in patients lacking a history of major arm or shoulder trauma. Radial neuropathy most often occurs in the setting of trauma, although many other uncommon causes have been described. With traumatic lesions, the prognosis for recovery is generally good, and for patients with persistent deficits, rehabilitation and surgical techniques may allow substantial functional improvement.

While there are a diverse number of indications for the potential use of cell and gene therapies in people, many of the medical conditions being treated need to consider some general clinical and surgical issues, not only in designing clinical trials, but also in the eventual application of the therapy if shown to be successful. Such issues include the precision of the diagnosis and stage of disease, the presence of significant comorbidity, as well as the challenges that may be encountered in trial designs involving the neurosurgical delivery of these advanced interventions. This chapter discusses details of these issues that have arisen particularly in the field of Parkinson disease and other forms of neurodegeneration, although the general principles and considerations discussed may be equally relevant to other neurologic and nonneurologic conditions.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is an adult-onset, inherited white matter disorder encompassing two previously identified clinicopathologically similar entities: pigmentary orthochromatic leukodystrophy (POLD) and hereditary diffuse leukoencephalopathy with spheroids (HDLS). In this chapter, we discuss how advances in our genetic understanding of the condition have further delineated three distinct clinical entities within ALSP, namely CSF1R-related ALSP, AARS2-related leukoencephalopathy (AARS2-L), and AARS (HDLS-S). We provide descriptions of the clinical, radiologic, pathologic, and pathophysiologic findings in each entity, detailing their similarities and differences, and discuss current and future treatment options where available.