低血糖颅脑损伤.ppt

低血糖症相关的神经系统损害 酒钢医院神经内、外科,Hypoglycemia in diabetesCryer PE et al.Diabetes Care.2003 June;26（6）:1902-1912.,一次严重的医源性低血糖或由此诱发的心血管事件可能会抵消一生维持血糖在正常范围所带来的益处,高血糖,低血糖,高,低,低血糖诊断标准,对具体患者来说，个体的低血糖标准可能有较大差异，症状与血糖值可以不同步当血糖小于2.8mmol/L，可诊断为低血糖症一般患者发生低血糖时出现低血糖（Whipple）三联征，即：低血糖症状和体征；血糖浓度低；血糖浓度升高至正常水平时症状消失或显著减轻,引起低血糖的原因,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,急性低血糖时的生理反应,增加拮抗激素的分泌，以拮抗胰岛素的作用，升高血糖使心血管系统发生相应变化，以利于葡萄糖在体内各种组织间的转运产生一系列预警症状，如饥饿，以迅速纠正低血糖,血糖水平及生理应答反应(1),血糖水平降低至 4.6 mmol/l时,胰岛素分泌受抑制血糖水平在 3.8mmol/l时，胰高血糖素、肾上腺素开始释放血糖水平在 3.0mmol/l时，开始出现低血糖症状血糖水平低于2.8mmol/l时，患者出现进行性认知能力下降血糖低于1.0mmol/l时，患者出现昏迷,血糖水平及生理应答反应(2),低血糖的表现,肾上腺交感神经症状 中枢神经症状,肾上腺交感神经症状,低血糖的症状:交感神经和肾上腺髓质兴奋的表现：焦急不安 情绪激动 手足颤抖、软弱 饥饿感 心慌 出汗 面色苍白 当血糖降至60ml/dl（3.3mmol/L）以下时就要注意是否出现上述症状。,中枢神经症状,如果血糖低于40mg/dl(2.2mmol/L),就可能出现下述症状：头痛 躁动 疲倦,可有幻觉 意识丧失 视物不清 语言迟钝 神经过敏 癫痫发作 是由于脑细胞葡萄糖供应不足所致。（通常低血糖发展很快）,中枢神经受抑的表现,血糖下降而持久所致。表现为中枢缺氧缺糖症群，越高级的中枢受抑制越早，恢复越迟。大脑皮层：意志朦胧，头痛头晕，嗜睡，精神失常。皮层下中枢：神志不清，躁动惊厥，瞳孔散大。延脑：昏迷，反射消失，呼吸浅弱，血压下降，瞳孔缩小，历时较久者，不易恢复。混合性：兼有上二种表现，多见。,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,低血糖的危害,1型糖尿病患者中至少4%是死于低血糖心血管系统功能神经系统其它：眼睛、肾脏社会活动（学习、就业等）,低血糖影响心血管系统功能,心率增加脉压增加静息期心肌缺血心绞痛心梗,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,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,低血糖影响大脑功能,脑干脊髓,Rostrocaudal sensitivity to neuroglycopenia,脑皮质海马,基底神经节前部丘脑,低血糖对脑损害的Himwich分期,分期 症状体征 动静脉氧压差 EEG,I期：大脑皮质损害II 期：脑皮质下间脑损害III 期：中脑损害IV 期：神经元损害V 期：神经元损害及生命中枢损害,定向力下降，吐词不清，嗜睡感觉分辨力丧失，对刺激无反应，但有自主性运动行为，心率快，瞳孔扩大张力性肌强直，眼非同向偏斜，跖反射异常转动头部可诱发四肢的伸肌痉挛昏迷、呼吸弱、心动过缓，眼球固定，瞳孔缩小，无对光反射，体温下降,6.82.61.8,慢波活动增加，节律(814cps)带慢波活动节律(14cps)节律极慢或无脑电波,Himwich HE.In:Brain Metabolism and Cerebral Disorders.Baltimore,William&Wilins,1951:257.,低血糖影响认知功能,记忆,注意力和集中,抽象思维,解释能力,信息处理速度,低血糖降低工作记忆,Deary et al.(2003)J.Neurol Neurosurg.Psych.74:278.,血糖正常,低血糖,低血糖影响驾驶能力,1型糖尿病患者驾驶模拟器研究（n=37）当血糖低于3.8 mmol/L时驾驶能力受损 撞车增多 加速和不恰当地制动 冲出路面 越过路面正中线 忽略STOP标识,Cox et al(2000)Diabetes Care 23:163.,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,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。,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,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,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,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。,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,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,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,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).,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).,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,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。,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,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.,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),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.,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.,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.,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.,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,低血糖对眼的影响,低血糖可显著减少玻璃体中的葡萄糖水平加剧缺血视网膜的损伤；严重低血糖可出现眼压突然下降，引起动脉破裂、出血。,低血糖对肾脏的影响,急性低血糖减少约22的肾血流；降低19的肾小球滤过率，加剧肾脏损害；低血糖的程度和危险因素的多少还影响慢性肾功能衰竭患者死亡率。,低血糖脑病的治疗,立即纠正低血糖查找诱发因素将神经功能损伤减少到最小促进神经功能恢复,低血糖脑病的治疗注意事项 对于低血糖脑病来说，最重要的治疗原则是防重于治,提高警惕及时发现，有效治疗。有以下临床表现者应怀疑低血糖存在：有较为明显的低血糖症状。有惊厥或发作性神经精神症状。有不明原因的昏迷。在相同的环境条件下，如禁食体力活动或餐后数小时，出现类似的综合性症状。有发生低血糖的危险者，如胰岛素或口服降糖药治疗的糖尿病患者，以及酗酒者等。当然，在确诊低血糖之前。必须及时进行详细检查，用准确可靠的血糖测定方法确定低血糖的存在。,低血糖的治疗,口服葡萄糖(20-30g)口服蔗糖进食物,患者有意识,静脉输注葡萄糖(如30-50ml 50%葡萄糖)1mg 胰高糖素肌注或者皮 下注射,患者意识障碍,每15-20分钟检查一次血糖水平确定低血糖恢复情况,静脉注射5%或者10%的葡萄糖，加用糖皮质激素,未见恢复,了解发生低血糖的原因对患者实施糖尿病教育建议患者注意经常进行血糖监 测，以避免低血糖再次发生,低血糖恢复,胶质的口服葡萄糖通常对缓解低血糖无效如果短期重复使用胰高糖素有可能使之失效磺脲类降糖药物引起低血糖时，小心使用胰高血糖素磺脲类降糖药物引起的低血糖持续时间较长,注意,低血糖脑病的预后,低血糖昏迷超过6h，即会有不可逆的脑组织损害，病愈后可遗留各种脑病后遗症严重者可因治疗无效而死亡。,