1、低血糖癥相關的神經系統損害 酒鋼醫院神經內、外科Hypoglycemia in diabetesCryer PE et al. Diabetes Care.2003 June;26（6）:1902-1912.一次嚴重的醫源性低血糖或由此誘發的心血管事件可能會抵消一生維持血糖在正常范圍所帶來的益處高血糖低血糖？高低低血糖診斷標準對具體患者來說，個體的低血糖標準可能有較大差異，癥狀與血糖值可以不同步當血糖小于2.8mmol/L，可診斷為低血糖癥一般患者發生低血糖時出現低血糖（Whipple）三聯征，即：低血糖癥狀和體征；血糖濃度低；血糖濃度升高至正常水平時癥狀消失或顯著減輕引起低血糖的原因最常見的

2、是降糖藥物使用不當所致。對胰島素過度敏感。胰島素過多：胰島素瘤，異位胰島素分泌瘤。反應性低血糖癥：早期糖尿病，功能性低血糖，營養性低血糖肝臟疾病中毒：藥物中毒，酒精中毒，大量食荔枝糖原累積病胃大部分切除術后腎上腺皮質或垂體前葉疾病急性低血糖時的生理反應增加拮抗激素的分泌，以拮抗胰島素的作用，升高血糖使心血管系統發生相應變化，以利于葡萄糖在體內各種組織間的轉運產生一系列預警癥狀，如饑餓，以迅速糾正低血糖血糖水平及生理應答反應(1)血糖水平降低至 4.6 mmol/l時,胰島素分泌受抑制血糖水平在 3.8mmol/l時，胰高血糖素、腎上腺素開始釋放血糖水平在 3.0mmol/l時，開始出現低血糖癥

3、狀血糖水平低于2.8mmol/l時，患者出現進行性認知能力下降血糖低于1.0mmol/l時，患者出現昏迷血糖水平及生理應答反應(2)5.04.03.0 2.01.00靜脈血糖水平(mmol/L)抑制內源性胰島素分泌4.6mmo/L拮抗激素分泌胰高血糖素腎上腺素3.8mmo/L開始出現低血糖癥狀自主神經癥狀3.2-2.8mmol/L神經生理功能異常喚醒障礙3.0-2.4mmol/L認知功能異常: 不能完成復雜任務2.8mmol/L腦電圖開始發生變化2.0mmol/L嚴重的低血糖患者發生意識障礙、驚厥及昏迷1.5mmol/L低血糖的表現腎上腺交感神經癥狀 中樞神經癥狀腎上腺交感神經癥狀低血糖的癥狀

4、:交感神經和腎上腺髓質興奮的表現： 焦急不安 情緒激動 手足顫抖、軟弱 饑餓感 心慌 出汗 面色蒼白 當血糖降至60ml/dl（3.3mmol/L）以下時就要注意是否出現上述癥狀。中樞神經癥狀如果血糖低于40mg/dl(2.2mmol/L),就可能出現下述癥狀： 頭痛 躁動 疲倦,可有幻覺 意識喪失 視物不清 語言遲鈍 神經過敏 癲癇發作 是由于腦細胞葡萄糖供應不足所致。（ 通常低血糖發展很快）中樞神經受抑的表現 血糖下降而持久所致。表現為中樞缺氧缺糖癥群，越高級的中樞受抑制越早，恢復越遲。 大腦皮層：意志朦朧，頭痛頭暈，嗜睡，精神失常。 皮層下中樞：神志不清，躁動驚厥，瞳孔散大。 延腦：昏迷

5、，反射消失，呼吸淺弱，血壓下降，瞳孔縮小，歷時較久者，不易恢復。 混合性：兼有上二種表現，多見。低血糖的不典型表現意識障礙合并抽搐，易誤診為癲癇精神癥狀，煩躁不安，易激惹，情緒激動，語無倫次，有罵人、打人，幻視有時可誤診為腦病及酒精中毒神志清楚，出現肢體，言語障礙，容易誤診為腦血管病昏迷，瞳孔不等大，對光反射遲鈍，易誤診為腦疝低血糖的危害1型糖尿病患者中至少4%是死于低血糖心血管系統功能神經系統其它：眼睛、腎臟社會活動（學習、就業等）低血糖影響心血管系統功能心率增加脈壓增加靜息期心肌缺血心絞痛心梗低血糖相關的神經系統損害低血糖的神經系統損害在有關著作和論文中被作為“神經低血糖”、“低血糖腦病”

6、“低血糖偏癱”，“低血糖昏迷”，“低血糖危象”，“缺糖性腦病”等等。有人認為為了便于對本病綜合征 的研究，稱做“低血糖的神經系統損害”較為合適低血糖性腦病可能發病機制低血糖引起交感神經興奮而導致腦血管痙攣原有腦動脈硬化的動脈狹窄所引起神經功能損傷低血糖引起神經系統的選擇受損低血糖影響大腦功能腦干脊髓Rostrocaudal sensitivity to neuroglycopenia腦皮質海馬基底神經節前部丘腦低血糖對腦損害的Himwich分期分期 癥狀體征 動靜脈氧壓差 EEGI期：大腦皮質損害II 期：腦皮質下間腦損害III 期：中腦損害IV 期：神經元損害V 期：神經元損害及生命中樞損害

7、定向力下降，吐詞不清，嗜睡感覺分辨力喪失，對刺激無反應，但有自主性運動行為，心率快，瞳孔擴大張力性肌強直，眼非同向偏斜，跖反射異常轉動頭部可誘發四肢的伸肌痙攣昏迷、呼吸弱、心動過緩，眼球固定，瞳孔縮小，無對光反射，體溫下降6.82.61.8慢波活動增加，節律(814cps)帶慢波活動節律(14cps )節律極慢或無腦電波Himwich HE.In: Brain Metabolism and Cerebral Disorders.Baltimore,William&Wilins,1951:257.低血糖影響認知功能記憶注意力和集中抽象思維解釋能力信息處理速度低血糖降低工作記憶Deary et a

8、l.(2003)J.Neurol Neurosurg.Psych.74:278.血糖正常 低血糖低血糖影響駕駛能力 1型糖尿病患者駕駛模擬器研究（n=37） 當血糖低于3.8 mmol/L時駕駛能力受損 撞車增多 加速和不恰當地制動 沖出路面 越過路面正中線 忽略STOP標識Cox et al (2000) Diabetes Care 23:163.低血糖腦病的診斷標準一多汗、面白、膚冷、手顫腿軟，全身無力。是低血糖刺激腎上腺素分泌增多所致意識障礙，嗜睡甚至昏迷，可用葡萄糖緩解癲癇發作，甚至出現癲癇持續狀態可有精神障礙，如舉止失常，定向力、識別力、記憶力減退，伴恐懼慌亂，躁狂，木僵局灶性神經系

9、統損害體征癥狀發生與血糖下降的程度、速度、持續時間及患者的機體反應性有關。當血糖下降快時，體內釋放大量腎上腺素，臨床表現為饑餓、出汗、心動過速、肌體震顫、無力等交感神經興奮癥狀。當血糖下降緩慢、歷時長，而致交感神經興奮癥狀不明顯，則臨床出現頭痛、頭暈、昏迷、抽搐、偏癱、尿失禁等中樞神經損害征象。低血糖反應可導致局灶神經損害，包括腦干征、偏癱、四肢癱、截癱和發作性舞蹈-徐動癥等因其發病突然，并有意識障礙或肢體癱瘓，且老年人多發，故易誤診為腦血管病。低血糖腦病的診斷標準二腦電圖呈彌漫性慢波，有癲癇發作者可出現癇性放電腦脊液檢查壓力增高，糖含量降低低血糖腦病的診斷標準Whipple三聯征空腹時具有低

10、血糖癥狀和體征血糖濃度在2.78mmol/L(50mg/dl)靜脈注射葡萄糖后癥狀立即緩解低血糖腦病影像診斷以往我國報道低血糖昏迷病例較多，除部分老年患者因合并腦梗死等顱腦CT或MRI有相應改變外，絕大多數報道稱患者的神經影像學無特殊異常因此不能單純依靠CT或MRI來診斷，應主要依靠臨床表現及血糖檢查來確診顱腦MRI對診斷具有重要價值頭重顱CT掃描對HE的診斷價值不大；MRI對嚴低血糖患者的診治有重要意義，尤其DWI序列由于葡萄糖減少導致大腦能量缺失和離子泵衰竭，水分子向細胞內運動和細胞外水容積顯著減少，導致細胞毒性水腫，水分子彌散障礙。可見雙側尾狀核和豆狀核對稱性或略長T1,長T2,Flai

11、r高信號，DWI高信號低血糖性腦病早期DWI檢查，其定位及定性敏感性比CT、常規MRI高，主要表現DWI呈高信號，表面彌散系數（ADC）值降低。低血糖腦損害具有一定的區域選擇性，細胞愈進化，對缺糖愈敏感尾狀核、豆狀核、大腦皮質、海馬和黑質是低血糖的敏感區域，最易受損也有研究提示敏感區域還包括胼胝體和皮質下白質。幾乎不累及丘腦，小腦及腦干有研究發現，嚴重低血糖患者病損一旦侵犯到皮質和基底節區，病變多不易恢復臨床癥狀和DWI異常可在短時間內逆轉者，病變多在胼胝體壓部，皮質下白質和內囊后肢提示DWI序列在一定程度上有助于判斷預后，胼胝體壓部受損者預后相對較好低血糖性腦病與缺血性腦血管病神經影像學兩個

12、顯著差別:一是缺血性腦血管病可見到小的出血點灶，而低血糖性腦病時沒有二是缺血性腦血管病可見到對稱性丘腦損害，而低血糖性腦病沒有大腦皮質雙側損害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 hyperinten

13、sity 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 nor

14、mal white matter (819 103 mm2/s).大腦皮質偏側損害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 a

15、ngiogram 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

16、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 la

17、ctate level (arrow1.3 ppm).大腦皮質損害，丘腦未累及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 hippoca

18、mpus 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新生兒低血糖MR表現病例1MR I 生

19、后34 h出現低血糖表現, 58 h入院, 血糖為1. 7mm ol/L。A D 為生后3 d所見。A, B分別為矢狀面T1W I和橫斷面T2W I, 可見頂枕葉T1W I低信號, 而T2W I改變不明顯; C為DW I, 可見頂枕葉皮層高信號, 提示明顯的細胞毒性水腫; D F為生后13 d T1W I( D) , T2W I( E )和DW I( F)圖像, 枕部可見明顯的T1W I低信號, T2W I高信號, 而DW I頂枕部轉為低信號, 提示皮層發生水腫壞死。皮質、基底節、腦室旁白質損害Fig. 1 ad (Patient 5) A57-year-old diabetic man wa

20、sfound 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 symmetr

21、ical 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內囊、放射冠損害Figure 1. Diffusion-weighted MRI on admission showing the hyperintensity lesions within the bilateral internal

22、 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.半卵圓中心非對稱損害Fig. 5 a, b (Patient 17) A 91-year-old diabetic ma

23、n 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、胼胝體損害Figure 1. A, Initial DWI (repetition time/

24、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.內囊、胼胝體損害Figure 1 (A) Diffusion-weighted

25、 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 o

26、btained 2 days after glucose infusion showing complete regression of the hyperintense lesions.海馬、皮質、胼胝體損害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 incr

27、eased 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

28、corpus callosum (arrowheads) .On (d) corresponding DW MR image, the hyperintense lesions are more prominent than they are on c.胼胝體、腦干損害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 lesio

29、ns 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. 胼胝體、白質彌漫損害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