系统性红斑狼疮中枢神经系统病变的诊断及治疗

目的 对系统性红斑狼疮（ＳＬＥ）患中枢神经系统病变（ＣＮＳ）的诊治经验进行总结,方法 对北京协和医院１７１例有ＣＮＳ的ＳＬＥ住院病例进行回顾性分析。结果（１）１７１例发病时ＳＬＥ病程为（２．２１±１．８７）年,１６３例（９５．３％）伴狼疮活动;（２）１５１例行脑脊液检查,异常１３８例（９１．４％）。其中蛋白,压力及白细胞增高分别为１１３．６９及５１例,糖降低仅６例;（３）对有ＣＮＳ的ＳＬＥ,头     

Swallowing: Neurophysiologic control of the esophageal phase

The esophageal phase of deglutition exhibits an independent neural control as compared to that for the pharynx and requires an interaction between central and peripheral neurons. Primary and secondary peristalsis depends upon a coordinated, sequentially organized neuronal drive in which both a brainstem pathway and a peripheral interganglionic network complement, duplicate, and supplement their individual control mechanisms. Sensory feedback from the pharynx and esophagus modifies motor neuron output to the esophagus both in direct reflex arcs and through a more complex brainstem interneuronal network. Sensory feedback directly affects ganglionic segmental reflexes that link at a peripheral level to coordinate peristalsis timed with relaxation of the caudal sphincter. The neuronal control of the esophagus requires an integrated central and peripheral output that effectively times the relaxation of the rostral and caudal sphincters with simultaneous sequential activation of the esophageal muscles in an aboral direction of peristalsis.     

Neurophysiology of swallowing in the aged

The neurophysiology of normal swallowing and its alterations related to age are reviewed. Clinical implications in health and disease are discussed.Presented in part at the Second Annual Scientific Meeting of the Dysphagia Research Society, October 22, 1993, Lake Geneva, WI, USA     

Symmetry and reproducibility of swallowing sounds

Cervical auscultation is being used more frequently in the clinical assessment of dysphagic patients. The present study was designed to assess symmetry and the reproducibility of swallowing sounds detected simultaneously from bilateral cervical sites. Symmetry of the swallowing sounds acquired using our method was verified because no significant differences were found for any parameters in both time and frequency domain analyses between swallowing sounds detected bilaterally. This result supports the use of a unilateral site for the detection of swallowing sounds. The reproducibility of swallowing sounds was assessed by a coefficient of variation. Results of this analysis suggest that one should evaluate the acoustic characteristics of swallowing sounds from repeated swallows rather than from one swallow.     

Central nervous system involvement as a major manifestation of rheumatoid arthritis

A 58-year-old woman with an 8-year history of seropositive rheumatoid arthritis was admitted with right hemiparesis, history of seizures, fever, weight loss and headaches. Her blood tests revealed the presence of rheumatoid factor, elevated C-reactive protein and anti-cyclic citrullinated peptide antibodies (>200 RU/ml). Examination of cerebrospinal fluid demonstrated pleocytosis (118 cells/mm³, predominantly lymphocytes) with elevated protein level (58 mg/dl); cultures were negative. Magnetic resonance imaging findings were suggestive for meningoencephalitis. Short course of high-dose corticosteroids and cyclophosphamide led to clinical improvement. Rheumatoid vasculitis was probably responsible for neurological symptoms.     

Optogenetic control of the enteric nervous system and gastrointestinal transit

Introduction: There are limited effective therapies available for improving gastrointestinal (GI) transit in mammals with intractable or chronic constipation. Current therapeutics to improve GI-transit usually require oral ingestion of therapeutic drugs, such as the serotonin receptor agonist prucalopride. However, most receptors are distributed all over the body and unsurprisingly drugs like prucalopride stimulate multiple organs, often leading to unwanted side effects. There is a desperate need in the community to improve GI-transit selectively without effects on other organs.

Areas covered: We performed a systematic review of the literature on Pubmed and report significant technical advances in optogenetic control of the GI-tract. We discuss recent demonstrations that optogenetics can be used to potently control the activity of subsets of enteric neurons. Special focus is made of the first recent demonstration that wireless optogenetics can be used to stimulate the colon in conscious, freely-moving, untethered mice causing a significant increase in fecal pellet output. This is a significant technical breakthrough with a major therapeutic potential application to improve GI-transit.

Expert opinion: The ability to selectively stimulate the ENS to modulate GI-transit in live mammals using light, avoids the need for oral consumption of any drugs and side effects; by stimulating only the GI-tract.     

Image quality and radiation levels in videofluoroscopy for swallowing studies: A review

Inexpensive video recording equipment coupled to conventional x-ray fluoroscopes is now in widespread use by clinicians for the evaluation of patients with swallowing disorders. The prevalence and simplicity of this apparatus have encouraged its use by clinical specialists who are often not specifically trained in the safe use of x-ray equipment, and this may not be in the best interest of either the patient or the examiner. This has prompted an overview of the operating principles of videofluorescopy equipment. The factors governing image quality are discussed as well as potential hazards and protective measures for both patients and operator. A method of estimating the radiation dose to sensitive tissues from a typical swallowing study is included.     

Central nervous system bleeding in patients with rare bleeding disorders

Summary. Central nervous system (CNS) bleeding is one of the most severe and debilitating manifestations occurring in patients with rare bleeding disorders (RBDs). The aim of this study was to retrospectively collect data on patients affected with RBDs who had CNS bleeding, to establish incidence of recurrence, death rate, neurological sequences, most frequent location, type of bleeding and efficacy of treatments. Results pertained to 36 CNS bleeding episodes in 24 patients with severe deficiency except one with moderate factor VII (FVII) deficiency. Six patients (25%) experienced a recurrence and two had more than one recurrence. Seven patients (29%) had an early onset of CNS bleeding before the first 2 years of life, others (71%) later in life. In 76% of cases, CNS bleeding was spontaneous. CNS bleeding was intracerebral in 19 cases (53%), extracerebral in 10 (28%) and both intracerebral and extracerebral in two cases (6%). Neurosurgery was performed in 11 cases, in association with replacement therapy in seven cases. Seizures were noted in four patients. Residual psychomotor abnormalities were seen in two patients. No death was recorded. To prevent recurrence, 17/24 patients (71%) were put on secondary prophylaxis. In conclusion, recurrence of CNS bleeding was confirmed to be relatively frequent in patients with severe FV, FX, FVII and FXIII deficiencies. Most patients were managed with replacement therapy alone, surgery being reserved for those with worsening neurological conditions. Our results indicate that some RBDs require early prophylactic treatment to prevent CNS bleeding. Optimal dosage and frequency of treatment need further evaluation.     

Central nervous system involvement in elderly patients with non-insulin-dependent diabetes mellitus

Summary We examined cognitive functions and central conduction velocities in 20 patients, over 63-year old, with NIDDM compared with 20 normal, age-matched controls. Mean conduction velocity of median nerve, was significantly lower in diabetics than in controls, but absolute values were within normal range. Neurological examination showed clinical signs of lower limbs neuroperipheral involvement. Only one cognitive subtest performance was abnormal whereas there was no impairment in central conduction velocities. In our study population, although median nerve conduction velocity values may introduce a bias of low peripheral neuropathy incidence, there was no evidence of a massive or progressive specific central nervous system involvement caused by NIDDM.     

Thermomechanical facilitation of swallowing evoked by electrical nerve stimulation in cats

Application of a cold metal probe to the anterior faucial pillar has been reported to improve swallowing in some patients with dysphagia. Although a variety of stimuli contribute to the initiation of swallowing, the effects of a controlled, cold-thermal stimulus combined with mechanical stimulation have not been examined. It is known that simultaneous stimulation of the glossopharyngeal nerve (IX) and the superior laryngeal nerve may summate to facilitate swallowing in the cat. The goal of this study was to determine whether thermomechanical stimulation of the mucosa innervated by IX would interact with threshold electrical stimulation of the internal laryngeal nerve (ILN) to augment the swallowing response in cats. Four experimental conditions were tested over 24 trials in 4 pentobarbital-anesthetized cats. These included electrical stimulation of ILN, mechanical stimulation of the anterior faucial pillar with a thermode at ambient (room) temperature, concurrent ambient-mechanical and electrical stimulation, and concurrent cold-mechanical and electrical stimulation. Tissue was cooled to 8.9°C during cold-mechanical-electrical stimulation and 25.3°C during ambient-mechanical-electrical and ambient-mechanical alone stimulation. Ambient-mechanical stimulation alone did not produce swallowing. However, both forms of thermomechanical-electrical stimulation elicited a significantly greater number of swallows than did electrical stimulation alone. Therefore, mechanical stimulation with a thermode was capable of modifying the swallowing response in neurologically intact cats. Differences between stimulation with a probe at ambient and at cold temperatures were not significant.     

Central nervous system infection following allogeneic hematopoietic stem cell transplantation

Objective/backgroundHere, we described the clinical characteristics and outcomes of central nervous system (CNS) infections occurring after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a single institution over the previous 6 years.MethodsCharts of 353 consecutive allogeneic transplant recipients were retrospectively reviewed for CNS infection.ResultsA total of 17 cases of CNS infection were identified at a median of 38 days (range, 10–1028 days) after allo-HSCT. Causative pathogens were human herpesvirus-6 (n = 6), enterococcus (n = 2), staphylococcus (n = 2), streptococcus (n = 2), varicella zoster virus (n = 1), cytomegalovirus (n = 1), John Cunningham virus (n = 1), adenovirus (n = 1), and Toxoplasma gondii (n = 1). The cumulative incidence of CNS infection was 4.1% at 1 year and 5.5% at 5 years.ConclusionMultivariate analysis revealed that high-risk disease status was a risk factor for developing CNS infection (p = .02), and that overall survival at 3 years after allo-HSCT was 33% in patients with CNS infection and 53% in those without CNS infection (p = .04).     

Central neural control of esophageal motility: A review

We review recent studies on the central neural control of esophageal motility, emphasizing the anatomy and chemical coding of esophageal pathways in the spinal cord and medulla. Sympathetic innervation of the proximal esophagus is derived primarily from cervical and upper thoracic paravertebral ganglia, whereas that of the lower esophageal sphincter and proximal stomach is derived from the celiac ganglion. In addition to noradrenaline, many sympathetic fibers in the esophagus contain neuropeptide Y (NPY), and both noradrenaline and NPY appear to decrease blood flow and motility. Preganglionic neurons innervating the cervical and upper thoracic ganglia are located at lower cervical and upper thoracic spinal levels. The preganglionic innervation of the celiac ganglion arises from lower thoracic spinal levels. Both acetylcholine (ACh) and enkephalin (ENK) have been localized in sympathetic preganglionic neurons, and it has been suggested that ENK acts to pre-synaptically inhibit ganglionic transmission. Spinal afferents from the esophagus are few, but have been described in lower cervical and thoracic dorsal root ganglia. A significant percentage contain calcitonin gene-related peptide (CGRP) and substance P (SP). The central distribution of spinal afferents, as well as their subsequent processing within the spinal cord, have not been addressed. Medullary afferents arise from the nodose ganglion and terminate peripherally both in myenteric ganglia, where they have been postulated to act as tension receptors, and, to a lesser extent, in more superficial layers. Centrally, these afferents appear to end in a discrete part of the nucleus of the solitary tract (NTS) termed the central subnucleus. The transmitter specificity of the majority of these afferents remains unknown. The central subnucleus, in turn, sends a dense and topographically discrete projection to esophageal motor neurons in the rostral portion of the nucleus ambiguus (NA). Both somatostatin- (SS) and ENK-related peptides have been localized in this pathway. Finally, motor neurons from the rostral NA innervate striated portions of the esophagus. In addition to ACh, these esophageal motor neurons contain CGRP, galanin (GAL), N-acetylaspartylglutamate (NAAG), and brain natriuretic peptide (BNP). The physiological effect of these peptides on esophageal motility remains unclear. Medullary control of smooth muscle portions of the esophagus have not been thoroughly investigated.     

Central nervous system vasculitis and polyneuropathy as first manifestations of hepatitis C

Sensory or motor peripheral neuropathy may be observed in a significant proportion of hepatitis C virus (HCV)-infected patients. However, central nervous system (CNS) involvement is uncommon, especially in cryoglobulin-negative subjects. We describe a case of peripheral neuropathy combined with an ischemic CNS event as primary manifestations of chronic HCV infection without cryoglobulinemia. Significant improvement was observed after antiviral therapy. We discuss the spectrum of neurological manifestations of HCV infection and review the literature.     

Central nervous system myelomatosis: review of the literature

Involvement of the central nervous system (CNS) in multiple myeloma (MM) is very uncommon; it has been observed in approximately 1% of the MM patients. This review summarizes the clinical and laboratory characteristics and treatment modalities of 109 patients with CNS myelomatosis (CNS MM) reported in the literature. CNS MM has a wide spectrum of neurological symptoms and signs. No guidelines for therapy of CNS MM are available, which has resulted in a large variation in the treatment schedules. Treatment options include intrathecal chemotherapy (IT), systemic chemotherapy (SC), cranial irradiation (CI) or a combination. The prognosis of CNS MM remains poor, with an overall median survival from the time of diagnosis to death of 2.0 months (range 0.1–25 months). Patients who were treated with CI had a significantly ( P  = 0.004) longer survival when compared with patients without CI.     

Speech-language pathology and dysphagia: A brief historical perspective

In the past decade, speech-language pathologists have taken a leading role in the management of services for patients with oropharyngeal dysphagia. This article presents the historical perspective of this role, the rationale for assuming the responsibility, and suggests directions for continued involvement.     

Central nervous system manifestations of Mycoplasma pneumoniae infections

Mycoplasma pneumoniae infection is associated with several manifestations from the central nervous system (CNS) such as encephalitis, aseptic meningitis, acute transverse myelitis, stroke, and polyradiculopathy. In the current paper epidemiologic, clinical, laboratory and treatment data on these manifestations are reviewed. The M. pneumoniae induced immune dysregulation and its contributing role in the pathogenesis of neurological insult is discussed. The recent introduction in clinical practice of newer molecular diagnostic techniques has helped in establishing a firmer association between M. pneumoniae infection and CNS disease especially encephalitis. Clinicians should be aware of the potential association between M. pneumoniae infection and several CNS manifestations. The role of various anti-microbial or immunomodulating therapies in treating such manifestations should be further explored.     

32例AIDS伴发中枢神经系统感染病人临床分析

目的分析艾滋病(AIDS)住院病人中,中枢神经系统感染的发病率、疾病谱及临床特点。方法对2009-2011年,在北京佑安医院住院治疗的AIDS伴发中枢神经系统感染病人的临床资料进行回顾总结,对其临床表现、诊治、转归等进行分析。结果 502例AIDS住院病人中,伴发中枢神经系统感染者32例,发生率6.4%。主要症状包括头痛23例(71.9%)、发热23例(71.9%)、呕吐20例(62.5%)、脑膜刺激征12例(37.5%)、肢体活动障碍9例(28.1%)、意识障碍7例(21.9%)等。这些病人的CD4细胞中位数为31/mm3,其中,≤100/mm3者27例,占总数的84.4%。诊断包括:隐球菌脑膜脑炎13例(40.6%),弓形体脑病10例(31.3%),结核性脑膜炎5例(15.6%),真菌性脑炎3例(9.4%),巨细胞病毒(CMV)脑炎1例(3.1%)。最终,32例病人中有22例(68.8%)治愈出院,5例(15.6%)死亡,5例(15.6%)未愈出院。结论 AIDS病人中枢神经系统感染以发热、头痛、呕吐、脑膜刺激征阳性等症状体征比较多见,主要发生于CD4细胞较低的病人,且病死率高,在临床中应引起重视。     

Central nervous system emergencies in haematological malignancies

Neurological emergencies are frequently catastrophic events in the course of haematological malignancies (HM) that, if not promptly recognized and treated, may lead to lethal outcomes or chronic sequelae. They may occur at any time during the disease course, but are more frequently observed following relapse. Practice guidelines are lacking in the management of most central nervous system (CNS) complications in HM. Herein we review the pathophysiology, presentation and treatment of elevated intracranial pressure, spinal cord compression, status epilepticus, neurovascular complications, CNS infection, leucostasis and hyperviscosity. Further, we discuss the expanding spectrum of neurological complications of old and novel treatments in HM.     

葡萄糖稳态的中枢调控作用机制——2014年美国糖尿病协会“杰出科学成就奖”演讲报告解读

2014年第74届美国糖尿病协会年会上,美国德克萨斯大学西南医学中心Joel K.Elmquist教授获得了杰出科学成就奖,并发表了关于“Claude Bernard是正确的——葡萄糖稳态的大脑调控(Claude Bernard Was Right——Brain Control of Glucose Homeostasis)”的获奖演讲.现对其演讲报告作一简短的解读,探讨中枢神经系统对葡萄糖稳态的调控作用机制.