Increased risk for demyelinating diseases in patients with inflammatory bowel disease

BACKGROUND & AIMS: Reports of multiple sclerosis (MS), demyelination, and optic neuritis (ON) associated with anti-tumor necrosis factor alpha therapy resulted in warnings on prescribing instructions for infliximab, etanercept, and adalimumab. However, the underlying relationship between IBD and these neurologic conditions has not been established. METHODS: We performed a retrospective cohort study and a retrospective cross-sectional study using 1988 to 1997 data from the General Practice Research Database. A total of 7988 Crohn's disease and 12,185 ulcerative colitis patients were matched for age, sex, and primary care practice to 80,666 randomly selected controls. In the cohort study, incident cases of MS, demyelination, and/or ON (MS/D/ON) had to occur at least 1 year after registration with the physician and after the diagnosis of IBD. In the cross-sectional study, the diagnosis of MS/D/ON could either precede or follow the IBD diagnosis. RESULTS: In the cohort study, the incidence of MS/D/ON was higher in patients with Crohn's disease and ulcerative colitis compared with their matched controls, reaching statistical significance for ulcerative colitis (ulcerative colitis incidence rate ratio [IRR], 2.63; 95% confidence interval, 1.29-5.15; Crohn's disease IRR, 2.12; 95% confidence interval, .94-4.50). In the cross-sectional study, MS/D/ON was more prevalent in patients with Crohn's disease and ulcerative colitis compared with their matched controls (Crohn's disease odds ratio, 1.54; 95% confidence interval, 1.03-2.32; ulcerative colitis odds ratio, 1.75; 95% confidence interval, 1.28-2.39). CONCLUSIONS: Demyelinating diseases occur more commonly among patients with IBD than among non-IBD patients. Future studies should clarify whether treatment with tumor necrosis factor alpha blockers results in further increased incidence of MS/D/ON among IBD patients.     

CPZ介导急性脱髓鞘小鼠海马中nestin的表达

目的:探讨双环己酮草酰二腙(cuprizone,CPZ)介导急性脱髓鞘小鼠海马中nestin的表达。方法:用掺入0.2%CPZ的普通饲料饲养C57BL/6小鼠6周,制备脱髓鞘模型,然后使用免疫荧光染色、q RT-PCR、Western Blot方法,检测小鼠脑内髓鞘脱失后海马中nestin的表达变化。结果:(1)体重称量结果显示:CPZ组体重明显低于对照组(P0.01);(2)免疫荧光结果显示:CPZ组海马CA区和DG区颗粒细胞层中nestin阳性细胞明显低于对照组分别为:P0.05,P0.01;(3)Western Blot和q RT-PCR实验结果显示:CPZ组海马中nestin蛋白和m RNA含量均明显低于对照组(P0.05)。结论:CPZ介导小鼠急性脱髓鞘后海马内nestin表达降低,提示髓鞘脱失可能会抑制nestin表达。     

MOG抗体脑脊髓炎1例分析并文献复习

目的：学习和讨论MOG抗体脑脊髓炎的临床特点、治疗方法及预后。方法：报道1例少见的MOG抗体 脑脊髓炎病例并复习相关文献。结果：该病例以癫痫为首发临床症状,影像学表现为皮质、深部灰质核团及 软脑膜受累,血清及脑脊液MOG抗体阳性,激素治疗后症状缓解明显。搜索既往MOG抗体脑脊髓炎病例报 道,检索出脑炎表现的成人患者病例61例。以急性播散性脑脊髓炎及脑干脑炎病例常见,治疗方法主要是免 疫治疗。结论：目前MOG抗体脑脊髓炎的病理机制尚不明确,临床特征、治疗及预后也存在不确定性。因 此,早期识别、及时治疗是获得更好预后的重要因素。     

渗透性脱髓鞘综合征的临床和影像学研究(附四例报道)

目的 探讨渗透性脱髓鞘综合征的临床和神经影像特点.方法 对4例渗透性脱髓鞘综合征患者的临床演变过程、CSF、头颅CT和MRI、EEG动态变化特点、治疗及预后进行分析.结果 4例患者均存在低钠血症,纠正后出现精神意识改变、构音和吞咽困难、四肢瘫痪、肌张力障碍等症状,临床过程有双相性.EEG出现一过性的重度异常.头颅CT及CSF均未见异常.MRI特征性影像晚于临床表现10 d以后出现,4例患者首次MRI均为阴性,7～13 d后复查才显示病灶.MRI示4例患者均存在脑桥外髓鞘溶解症病灶,T1WI加权低信号,T2WI加权高信号,对称性地累及双侧尾状核、豆状核、丘脑、脑岛叶皮质、海马头部等部位,其中3例同时存在脑桥中央髓鞘溶解症改变,呈脑桥基底部位对称性T1低、T2高信号的蝶形病灶;Flair加权异常信号更清楚.3例有好转或痊愈,其中1例遗留明显肌张力障碍.结论 渗透性脱髓鞘综合征与慢性低钠血症有关,合并低血钾、低血氯时可能更易发生.治疗时应尽量避免过快纠正,临床病程具有双相性.MRI的特征性改变出现较迟,复查MRI是非常必要的.     

中枢神经系统炎性脱髓鞘损伤髓鞘再生的细胞学治疗

多发性硬化（MS）损伤的病理特征是髓鞘脱失。髓鞘再生近年来被认为是自身免疫性脱髓鞘疾病，尤其是MS治疗中非常有前景的方向。髓鞘再生治疗可分为内源性和外源性，所以大量的临床和实验研究都集中于通过外源性移植细胞或通过促进内源性再生机制来获得中枢神经系统脱髓鞘区域的髓鞘再生，并均取得一定的成功。本文对近年来MS髓鞘再生的细胞学治疗的现状和神经科学背景及再生髓鞘治疗的将来可能发展方向进行了评述。     

Diffusion tensor imaging detects axonal injury and demyelination in the spinal cord and cranial nerves of a murine model of globoid cell leukodystrophy

Globoid cell leukodystrophy is an inherited neurodegenerative disorder caused by a deficiency of the lysosomal enzyme galactosylceramidase. In both human patients and the authentic murine Twitcher model, pathological findings include demyelination as well as axonal damage in both the central and peripheral nervous system. Diffusion tensor imaging (DTI) has emerged as a powerful noninvasive technique that is sensitive to these white matter disease processes. Increases in radial diffusivity (λ?) and decreases in axial diffusivity (λ∥) correlate with histopathological evidence of demyelination and axonal damage, respectively. Compared to age‐matched, normal littermates, DTI of optic nerve and trigeminal nerve in end‐stage Twitcher mice displayed a statistically significant increase in λ? and decrease in λ∥, consistent with previously characterized demyelination and axonal damage in these regions. In the Twitcher spinal cord, a statistically significant decrease in λ∥ was identified in both the dorsal and ventrolateral white matter, relative to normal controls. These results were consistent with immunofluorescence evidence of axonal damage in these areas as detected by staining for nonphosphorylated neurofilaments (SMI32). Increase in λ? in Twitcher spinal cord white matter relative to normal controls reached statistical significance in the dorsal columns and approached statistical significance in the ventrolateral region. Correlative reduced levels of myelin basic protein were detected by immunofluorescent staining in both these white matter regions in the Twitcher spinal cord. Fractional anisotropy, a nonspecific but sensitive indicator of white matter disease, was significantly reduced in the optic nerve, trigeminal nerve, and throughout the spinal cord white matter of Twitcher mice, relative to normal controls. This first reported application of spinal cord DTI in the setting of GLD holds potential as a noninvasive, quantitative assay of therapeutic efficacy in future treatment studies. Copyright © 2009 John Wiley & Sons, Ltd.     

Movement disorders and the osmotic demyelination syndrome

With the advent of MRI, osmotic demyelination syndromes (ODS) are increasingly recognised to affect varied sites in the brain in addition to the classical central pontine lesion. Striatal involvement is seen in a large proportion of cases and results in a wide variety of movement disorders. Movement disorders and cognitive problems resulting from ODS affecting the basal ganglia may occur early in the course of the illness, or may present as delayed manifestations after the patient survives the acute phase. Such delayed symptoms may evolve over time, and may even progress despite treatment. Improved survival of patients in the last few decades due to better intensive care has led to an increase in the incidence of such delayed manifestations of ODS. While the outcome of ODS is not as dismal as hitherto believed – with the acute akinetic-rigid syndrome associated with striatal myelinolysis often responding to dopaminergic therapy – the delayed symptoms often prove refractory to medical therapy. This article presents a review of the epidemiology, pathophysiology, clinical features, imaging, and therapy of movement disorders associated with involvement of the basal ganglia in ODS. A comprehensive review of 54 previously published cases of movement disorders due to ODS, and a video recording depicting the spectrum of delayed movement disorders seen after recovery from ODS are also presented.     

A case of inflammatory demyelinating polyradiculoneuropathy associated with T-cell lymphoma

Malignant lymphoma may present prominent peripheral nervous system disorders with variable etiologies. We describe a patient who presented with chronic relapsing polyradiculoneuropathy accompanied by right facial nerve palsy. Gadolinium enhancement of the right facial nerve and cervical spinal roots was noted on magnetic resonance imaging (MRI). Sural nerve biopsy specimens showed mononuclear cell infiltration around the vessels in the epineurium. Histopathological and immunohistochemical investigations of sural nerve specimens revealed perivascular infiltration of lymphocytes with T-cell dominancy. No apparent direct invasion of lymphoma cells was seen. The results of nerve conduction studies, sural nerve biopsy and cerebrospinal fluid examination were suggestive of immune-mediated inflammatory demyelinating neuropathy. The chronic and relapsing fashion and unique radiological findings in our patient expand on the previously reported features of peripheral neuropathy associated with peripheral T-cell lymphoma.