缺血性脱髓鞘

我们对表现为缺血性脱髓鞘的白质损害的发病机制和潜在临床意义的理解已经取得了一定的进展。脑CT扫描上的低密度损害被称为脑白质疏松，最常见于脑室周围，也常见于半卵圆中心。在过去几年，尝试使用“Binswanger病”一词来描述这种损害的神经系统结局并不少见。随着脑MRI扫描技术的出现，使我们对这种损害的描述更为精细，MRI对这种白质区域信号强度增高非常敏感，特别是T2加权和液体衰减翻转恢复序列（FLAIR）扫描。阐明这种在老年人群中相对常见现象的临床特征仍然具有挑战性。最近的研究以一种类似多发性硬化所见的方式对损害负荷进行了研究。白质疾病的一种独特临床相关模型是伴皮质下梗死和白质脑病的常染色体显性遗传脑动脉病（CADASIL），它结合了小血管病变的潜在成分（导致进行性神经功能缺损），与偏头痛（也与白质损害有关）常常有一定的联系。然而，与微血管病（它似乎是缺血性脱髓鞘的核心）相关的最常见的致病因素仍然是高血压。我们如何能很好地将这种脑终末器官损害的各种致病机制联系在一起将决定我们如何能对这种老年人群的常见神经功能缺损病变进行有效地干预。     

Ischemic demyelination

White matter lesions representing ischemic demyelination have evolved in terms of our understanding of their pathogenesis and potential clinical significance. Low density lesions on CT brain scan, most commonly seen in the periventricular region, also frequently seen in the centrum semiovale, have been termed 'leukoaraiosis'. In the past years, it was not uncommon at all to hear the term 'Binswanger's disease' used in an attempt to define the neurological sequelae of such lesions. Further refinement came with the advent of magnetic resonance imaging (MRI) brain scan which is particularly sensitive to such white matter areas of increased signal intensity, which tend to be seen particularly well on T2-weighted and fluid attenuation inversion recovery (FLAIR) scans.The major challenge has been to correlate the clinical attributes with such relatively frequent findings in the elderly population. Recent studies have looked at lesion load in a fashion analogous to that seen with multiple sclerosis. A particularly relevant clinical model for white matter disease is cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) which combines the potential components of small vessel disease, resulting in progressive neurological deficit, with a common association with migraine which can also be associated with white matter lesions. However, the most common pathogenic factor associated with the microangiopathy, which appears to be at the heart of ischemic demyelination, continues to be hypertension. How well we are able to tie in the various pathological mechanisms associated with this end organ damage of the brain will determine how well we can arrive at effective interventions for a common contributor to neurological deficits in the elderly.     

Ischemic neuropathy

Ischemia plays an important role in the development of neuropathies associated with various disorders, such as peripheral vascular occlusive diseases, necrotizing vasculitides, diabetes mellitus and nerve compression or trauma. Although a multiple mononeuropathy or an asymmetrical polyneuropathy is the usual clinical presentation of ischemic neuropathy, some patients present with a neuropathy that is mainly distal and symmetrical. Pathologically, nerve ischemia results in focal or multifocal central fascicular or sector fiber degeneration. These ischemic lesions tend to begin at mid-upper arm or midthigh level, which is the watershed zone of poor perfusion, and become more diffuse distally. Nerve ischemia at the level of distal small fascicles often induces sub-perineurial crescent lesion rather than central fascicular fiber degeneration. Physiologically, reduced nerve blood flow with endoneurial hypoxia has been demonstrated in experimental diabetic and galactose neuropathies. Endoneurial ischemia/hypoxia in galactose neuropathy appears to be due to increased intercapillary distances and constriction of trans-perineurial vessels resulting from endoneurial edema. Although acute ischemic neuropathy has been well investigated, little is known about functional or structural responses of peripheral nerve to chronic ischemia.     

Reduced Ischemic Lesion Growth with Heparin in Acute Ischemic Stroke

Objective: The role of heparin in acute ischemic stroke is controversial. We investigated the effect of heparin on ischemic lesion growth. Methods: Data were analyzed on nonthrombolyzed ischemic stroke patients in whom diffusion-weighted imaging (DWI)/perfusion-weighted imaging (PWI) MRI was performed less than 12 hours of last known well and showed a PWI-DWI lesion mismatch, and who underwent follow-up neuroimaging at least 4 days after admission. Lesion growth was assessed by (1) absolute lesion growth and (2) percentage mismatch lost (PML). Univariate and multivariate regression analysis, and propensity score matching, were used to determine the effects of heparin on ischemic lesion growth. Results: Of the 113 patients meeting study criteria, 59 received heparin within 24 hours. Heparin use was associated with ～5-fold reductions in PML (3.5% versus 19.2%, P = .002) and absolute lesion growth (4.7 versus 20.5 mL, P = .009). In multivariate regression models, heparin independently predicted reduced PML (P = .04) and absolute lesion growth (P = .04) in the entire cohort, and in multiple subgroups (patients with and without proximal artery occlusion; DWI volume greater than 5 mL; cardio-embolic mechanism; DEFUSE-3 target mismatch). In propensity score matching analysis where patients were matched by admission NIHSS, DWI volume and proximal artery occlusion, heparin remained an independent predictor of PML (P = .048) and tended to predict absolute lesion growth (P = .06). Heparin treatment did not predict functional outcome at discharge or 90 days. Conclusion: Early heparin treatment in acute ischemic stroke patients with PWI-DWI mismatch attenuates ischemic lesion growth. Clinical trials with careful patient selection are warranted to investigate the potential ischemic protective effects of heparin.     

短暂性脑缺血发作对脑缺血耐受的影响

目的 探讨短暂性脑缺血发作（TIA）在脑缺血耐受方面的临床意义。方法 选择30例TIA后72h内发生脑梗死的患者为试验组（TIA组）,并随机选择30例无TIA史的脑梗死患者作对照组。结果 TIA组和脑梗死组在脑梗死体积、治疗前与治疗后15d,30d,90d的欧洲卒中量表（ESS）评分方面存在统计学差异（8.2 ml vs 10.6 ml;62±22 vs 58±24;70±28 vs 66±32;80±20 vs 76±24;82±18 vs 77±23; P均<0.05）。结论 TIA后发生脑梗死对减轻脑细胞损伤有一定临床意义。     

Ischemic optic neuropathy

Ischemic optic neuropathies (IONs) are the most frequent acute optic neuropathy in patients older than 50 years. They are classified according to the location of the ischemic damage into anterior ION and posterior ION. Ischemic optic neuropathies may also be categorized based on the presence or absence of temporal arteritis as an underlying etiology. Anterior ION presents with sudden, painless visual loss developing over hours to days. Examination findings usually include decreased visual acuity, a visual field defect, color vision loss, a relative afferent pupillary defect, and a swollen optic nerve head. Posterior ION occurs in arteritic, nonarteritic, and surgical settings. It is characterized by acute vision loss without initial disc edema but with subsequent optic disc atrophy.     

Ischemic heart disease

Ischemic Heart Disease (IHD) is the single most important preventable disease in the U.S. Risk factors for the development of IHD have been well described, and treatment strategies for the primary, secondary, and tertiary prevention of this disease are available. Because of the prevalence of IHD, and known benefits of intervention, psychiatrists should be familiar with screening and treatment. This paper describes the screening and intervention strategies suitable for psychiatrists caring for patients at risk for IHD.     

Ischemic optic neuropathy

ION typically affects the older population with a sudden decrease in vision, altitudinal visual field loss, and a swollen optic nervehead. Systemic hypertension and diabetes mellitus are the most commonly associated medical problems. Occlusion of the posterior ciliary arterial blood supply to the retrolaminar optic nerve leads to axoplasmic stasis and further compromise of vessels in the nerve substance, which causes the typical funduscopic appearance. Although there is no recognized medical treatment that can reverse the visual loss, a recent report suggests optic nerve sheath decompression for a select group of patients with a gradual decline in vision due to ION may be beneficial. When ION occurs in persons less than 50 years of age, such etiologies as juvenile diabetes mellitus, antiphospholipid antibody-associated clotting disorders, collagen-vascular disease, and migraines should be considered. Rarely, complications of intraocular surgery or acute blood loss may cause an ischemic event in the optic nerve.     

Ischemic optic neuropathies

PURPOSE OF REVIEW: To review recent clinical data on ischemic optic neuropathies, which are some of the most frequently encountered optic neuropathies. These disorders include nonarteritic anterior ischemic optic neuropathy, arteritic anterior ischemic optic neuropathy, and posterior ischemic optic neuropathy. RECENT FINDINGS: Recent studies have facilitated our understanding of the natural history of visual loss, recovery, and recurrence in these disorders. Additionally, the value of various diagnostic techniques and treatment options, particularly for arteritic anterior ischemic neuropathy, has been clarified. SUMMARY: Application of the studies described in this paper should allow the clinician to more accurately diagnose ischemic optic neuropathies and counsel the patient with regard to appropriate management, prognosis for visual recovery and future risk of recurrence.     

Ischemic monomelic neuropathy

Ischemic monomelic neuropathy (IMN) is an infrequently recognized type of ischemic neuropathy produced by the shunting of blood away from, or the acute noncompressive occlusion of, a major proximal limb artery. IMN consists of multiple axonal-loss mononeuropathies that develop acutely and simultaneously in the distal portion of a limb. We found stereotyped clinical and EMG features in 14 patients. In six the IMN was thromboembolic in nature, whereas in eight it was due to various vascular surgical procedures. Our experience with IMN suggests that distal axonal infarction can occur without significant muscle necrosis, supporting the hypothesis that in humans the distal nerve fibers are more vulnerable than muscle to acute noncompressive limb ischemia.     

Ischemic tolerance.

A brief period of cerebral ischemia confers transient tolerance to a subsequent ischemic challenge in the brain. This phenomenon of ischemic tolerance has been confirmed in various animal models of forebrain ischemia and focal cerebral ischemia. Since the ischemic tolerance afforded by preceding ischemia can bring about robust protection of the brain, the mechanism of tolerance induction has been extensively studied. It has been elucidated that ischemic tolerance protects neurons, and at the same time, it preserves brain function. Further experiments have shown that metabolic and physical stresses can also induce cross-tolerance to cerebral ischemia, but the protection by cross-tolerance is relatively modest. The underlying mechanism of ischemic tolerance still is not fully understood. Potential mechanisms may be divided into two categories: (1) A cellular defense function against ischemia may be enhanced by the mechanisms inherent to neurons. They may arise by posttranslational modification of proteins or by expression of new proteins via a signal transduction system to the nucleus. These cascades of events may strengthen the influence of survival factors or may inhibit apoptosis. (2) A cellular stress response and synthesis of stress proteins may lead to an increased capacity for health maintenance inside the cell. These proteins work as cellular "chaperones" by unfolding misfolded cellular proteins and helping the cell to dispose of unneeded denatured proteins. Recent experimental data have demonstrated the importance of the processing of unfolded proteins for cell survival and cell death. The brain may be protected from ischemia by using multiple mechanisms that are available for cellular survival. If tolerance induction can be manipulated and accelerated by a drug treatment that is safe and effective enough, it could greatly improve the treatment of stroke.