血糖相关脑病

1,血糖相关脑损害,湘雅医院李国良,2,低血糖相关的神经系统损害,低血糖相关的神经系统损害低血糖的神经系统损害在有关著作和论文中被作为“神经低血糖”、“低血糖脑病”“低血糖偏瘫”，“低血糖昏迷”，“低血糖危象”，“缺糖性脑病”等等。有人认为为了便于对本病综合征 的研究，称做“低血糖的神经系统损害”较为合适,3,低血糖脑病的诊断标准一,多汗、面白、肤冷、手颤腿软，全身无力。是低血糖刺激肾上腺素分泌增多所致意识障碍，嗜睡甚至昏迷，可用葡萄糖缓解癫痫发作，甚至出现癫痫持续状态可有精神障碍，如举止失常，定向力、识别力、记忆力减退，伴恐惧慌乱，躁狂，木僵局灶性神经系统损害体征,4,症状发生与血糖下降的程度、速度、持续时间及患者的机体反应性有关。当血糖下降快时，体内释放大量肾上腺素，临床表现为饥饿、出汗、心动过速、肌体震颤、无力等交感神经兴奋症状。当血糖下降缓慢、历时长，而致交感神经兴奋症状不明显，则临床出现头痛、头晕、昏迷、抽搐、偏瘫、尿失禁等中枢神经损害征象。低血糖反应可导致局灶神经损害，包括脑干征、偏瘫、四肢瘫、截瘫和发作性舞蹈-徐动症等因其发病突然，并有意识障碍或肢体瘫痪，且老年人多发，故易误诊为脑血管病。,5,低血糖脑病的诊断标准二,脑电图呈弥漫性慢波，有癫痫发作者可出现痫性放电脑脊液检查压力增高，糖含量降低,6,低血糖脑病的诊断标准,Whipple三联征空腹时具有低血糖症状和体征血糖浓度在2.78mmol/L(50mg/dl)静脉注射葡萄糖后症状立即缓解,7,低血糖的不典型表现,意识障碍合并抽搐，易误诊为癫痫精神症状，烦躁不安，易激惹，情绪激动，语无伦次，有骂人、打人，幻视有时可误诊为脑病及酒精中毒神志清楚，出现肢体，言语障碍，容易误诊为脑血管病昏迷，瞳孔不等大，对光反射迟钝，易误诊为脑疝,8,引起本病的原因,最常见的是降糖药物使用不当所致。对胰岛素过度敏感。胰岛素过多：胰岛素瘤，异位胰岛素分泌瘤。反应性低血糖症：早期糖尿病，功能性低血糖，营养性低血糖肝脏疾病中毒：药物中毒，酒精中毒，大量食荔枝糖原累积病胃大部分切除术后肾上腺皮质或垂体前叶疾病,9,低血糖性脑病可能发病机制,低血糖引起交感神经兴奋而导致脑血管痉挛原有脑动脉硬化的动脉狭窄所引起神经功能损伤低血糖引起神经系统的选择受损,10,低血糖脑病影像诊断,以往我国报道低血糖昏迷病例较多，除部分老年患者因合并脑梗死等颅脑CT或MRI有相应改变外，绝大多数报道称患者的神经影像学无特殊异常因此不能单纯依靠CT或MRI来诊断，应主要依靠临床表现及血糖检查来确诊,11,颅脑MRI对诊断具有重要价值,头重颅CT扫描对HE的诊断价值不大；MRI对严低血糖患者的诊治有重要意义，尤其DWI序列由于葡萄糖减少导致大脑能量缺失和离子泵衰竭，水分子向细胞内运动和细胞外水容积显著减少，导致细胞毒性水肿，水分子弥散障碍。可见双侧尾状核和豆状核对称性或略长T1,长T2,Flair高信号，DWI高信号低血糖性脑病早期DWI检查，其定位及定性敏感性比CT、常规MRI高，主要表现DWI呈高信号，表面弥散系数（ADC）值降低。,12,低血糖脑损害具有一定的区域选择性，细胞愈进化，对缺糖愈敏感尾状核、豆状核、大脑皮质、海马和黑质是低血糖的敏感区域，最易受损也有研究提示敏感区域还包括胼胝体和皮质下白质。几乎不累及丘脑，小脑及脑干目前认为，天门冬氨酸的区域性表达和N-甲基-D-天（门）冬氨酸（NMDA）受体的分布与HE病变的高度选择性关系密切,13,有研究发现，严重低血糖患者病损一旦侵犯到皮质和基底节区，病变多不易恢复临床症状和DWI异常可在短时间内逆转者，病变多在胼胝体压部，皮质下白质和内囊后肢提示DWI序列在一定程度上有助于判断预后，胼胝体压部受损者预后相对较好,14,低血糖性脑病与缺血性脑血管病神经影像学两个显著差别:,一是缺血性脑血管病可见到小的出血点灶，而低血糖性脑病时没有二是缺血性脑血管病可见到对称性丘脑损害，而低血糖性脑病没有,15,大脑皮质双侧损害,Fig 1. Case 1, a 65-year-old man in a diabetic coma with seizures.A, Fast spin-echo milliseconds/110 fluid attenuated inversion recovery (9000 milliseconds effective/2200 milliseconds TR/TE/TI) MR image shows bilateral hyperintensity of thecortex over the temporal and occipital lobes.B and C, Diffusion-weighted (10000/105, b value 1000 seconds/mm2) MR images showing corresponding hyperintensity in the cortex.D and E, ADC maps at the same levels as B and C show decreased ADC in these lesions (618 103 mm2/s) compared with normal white matter (819 103 mm2/s).,16,大脑皮质偏侧损害,Images in 26-year-old man (patient 6) found unconscious, with a Glasgow Coma Scale score of 7, and not moving left side. (a) DW MR image shows confluent hyperintense lesions in the right inferior frontal,insular, and posterior temporal lobe cortices. (b) MR angiogram shows increased vascularity of the right middle cerebral artery branches (arrow) compared with the normal left side, suggesting augmented collateral flow. (c) Relative cerebral blood volume map shows no noticeable decrease in the abnormal right cerebral hemisphere; blood volume was in fact increased by 20%25%, a finding that is also suggestive of maximalvasodilatation (see text). (d) Graph of single-oxel MR spectroscopic data in affected right cerebral cortex shows decreased N-acetylaspartate (NAA) level, preserved choline (Cho) and creatine (Cr) levels, and no evidence of abnormal lactate level (arrow1.3 ppm).,17,大脑皮质损害，丘脑未累及,Diffusion-weighted magnetic resonance (MR) imaging (A) and T2-weighted MR imaging (B) showed a diffuse cortical high signal. The brainstem,cerebellum, and thalamus were spared as were the dorsofrontal cortex and occipital poles. The signal change in the hippocampus was relatively small on diffusion-weighted MR imaging. On T2-weighted MR imaging, a focal high-signal lesion was seen in the thalamus bilaterally (more prominent on the left side) and in the centrum semiovale. Diffuse white matter lesions were seen on the T2-weighted MR image,18,新生儿低血糖MR表现,病例1MR I 生后34 h出现低血糖表现, 58 h入院, 血糖为1. 7mm ol/L。A D 为生后3 d所见。A, B分别为矢状面T1W I和横断面T2W I, 可见顶枕叶T1W I低信号, 而T2W I改变不明显; C为DW I, 可见顶枕叶皮层高信号, 提示明显的细胞毒性水肿; D F为生后13 d T1W I( D) , T2W I( E )和DW I( F)图像, 枕部可见明显的T1W I低信号, T2W I高信号, 而DW I顶枕部转为低信号, 提示皮层发生水肿坏死。,19,皮质、基底节、脑室旁白质损害,Fig. 1 ad (Patient 5) A57-year-old diabetic man wasfound in a coma 6 h after he was last seen. Glucose level was 16 mg/dL at presentation.Fluid-attenuated inversionrecovery image (a) on the day ofadmission shows slightlyincreased signal intensity in thecerebral cortex and basalganglia. Diffusion-weightedimages (b, c) clearly showbilaterally symmetrical hyperintense lesions in the cerebral cortex, basal ganglia, and periventricular white matter(arrows). ADC map (d) obtained at the same level as c shows corresponding reduced ADC,20,内囊、放射冠损害,Figure 1. Diffusion-weighted MRI on admission showing the hyperintensity lesions within the bilateral internal capsule, corona radiata, and frontoparietal cortex. Note that bilateral hippocampi do not disclose any hyperintensity lesions.,Figure 2. Diffusion-weighted MRI 10 days after glucose infusion showing regression of the hyperintensity lesions.,21,半卵圆中心非对称损害,Fig. 5 a, b (Patient 17) A 91-year-old diabetic man admitted for drowsiness for 10 h. Glucose level was 24 mg/dL at presentation .Diffusion-weighted image (a) on the day of admission shows focal area of unilateral hyperintense lesion in the left centrum semiovale (arrows) with reduced ADC value (b),22,放射冠、胼胝体损害,Figure 1. A, Initial DWI (repetition time/echo time/ 4100/96/90;1000 s/mm2; field of view 230 mm; matrix: 128128) withincreased signal intensities in bilateral corona radiata and splenium.B, Initial ADC maps with signal reduction also in bilateralcorona radiata and splenium corresponding to DWI images.,23,内囊、胼胝体损害,Figure 1 (A) Diffusion-weighted imaging (DWI) on admission showing hyperintense lesions in the splenium of the corpus callosum and the bilateral posterior limbs of the internal capsules. (B) DWI obtained 2 h after glucose infusion showing almost full recovery except for a small part of the spleniumof the corpus callosum.(C) DWI obtained 2 days after glucose infusion showing complete regression of the hyperintense lesions.,24,海马、皮质、胼胝体损害,Figure 2: Images in 51-year-old man (patient 2) found unconscious, with a Glasgow Coma Scale score of 7 and withdrawal to pain. (a) Fluid-attenuated inversion recovery and (b)DWMRimages show increased signal intensity in the head, body, and tail of the hippocampus bilaterally (arrowheads) and in the cerebralcortex (arrow). (c) T2-weightedMRimage shows bilateral patchy hyperintense lesions in the cerebral cortex ,including the insula (arrow). There is also involvement of the splenium of the corpus callosum (arrowheads) .On (d) corresponding DW MR image, the hyperintense lesions are more prominent than they are on c.,25,胼胝体、脑干损害,Figure 4: Images in 61-year-old man (patient 8) admitted for drowsiness, confusion, left hemiparesis, and slurred speech. (a, b) DW MR images show hyperintense lesions in the left hemipons and the splenium of the corpus callosum. (c, d) Repeat DW MR images obtained 36 hours later show no change in the pontine lesion,but reversal of the callosal abnormality.,26,胼胝体、白质弥漫损害,Fig. 3 ad (Patient 14) A32-year-old woman was found in a coma 2 days after she was last seen. Glucose level was 33 mg/dL at presentation.Diffusion-weighted images(a, b) on the day of admission show bilaterally symmetrical confluent hyperintense lesions in the periventricular andsubcortical white matters. There are also involvements of thecorpus callosum and internal capsule. ADC maps (c, d) at thesame levels as a and b show decreased ADC in these lesions ;the lesions spared the cortical and deep gray matter,27,Diffuse cortical leisions ,had a poor outcomeWhite matter abnormalities ,made a complete recovery,28,高血糖性脑损害,糖尿病控制不好，血糖不当地上升时，常有一些神经性异常，包括瞻妄昏迷抽搐中风似症状有少数病患则会发生半边芭蕾症（hemiballism）,29,非酮症性高血糖脑损害临床和影像学特征,糖尿病性偏侧舞蹈症多见于糖尿病控制不佳的高血糖患者，糖尿病酮症及非酮症均可发病血糖水平通常超过200mg/dl临床表现为舞蹈症、癫痫、认知功能障碍等治疗糖尿病预后良好通常影响单侧或双侧的尾状核和豆状核，均累及壳核。平挡CT呈高密度，MR上T1高信号，部分强化，T2可以是正常或稍高或低信号，无水肿征象。MRS显示高乳酸峰和低Cr,30,非酮症性高血糖偏侧舞蹈症(单侧),患者，男，72岁。因右侧肢体不自主舞动2个月于2009年8月17日入院。既往：糖尿病史8年，间断口服二甲双胍，血糖控制不稳定。空腹血糖18.47mmol/L，尿酮体阴性，尿糖(+） ，血铜蓝蛋白035gL ，KF环阴性。头MRI T1WI示：左侧豆状核(以壳核为主)及尾状核头T1相呈高信号,31,非酮症性高血糖偏侧舞蹈症典型病人,32,非酮症性高血糖偏侧舞蹈症(单侧),男，73岁，右侧肢体不自主运动6天，血糖37.2mmol/dl,尿糖（+）,33,非酮症性高血糖合并舞蹈症临床特点,1、见于糖尿病患者；2、以急起的舞蹈样投掷运动为特征，一般无神经系统其他的症状和体征；3、发病时血糖高，但血酮体阴性；4、CT基底节区密度稍高，MRI表现为短T1信号，T2像改变不明显，也可出现稍短T2的表现；5、疾病病理不明，可能与高血糖导致局部血管通透性增加导致血管渗血有关，也可能与高血糖所致的局部代谢障碍有关；6、首先应尽快纠正高血糖，同时可予氟哌啶醇等对症处理；7、预后：纠正高血糖后大部分病人症状消失 。,34,对MRI信号形成的多种认识,有人认为，这种MRI的信号变化可以用该部位的点状出血及随后的高铁血红蛋白形成和含铁血红素的沉积来解