再见，霍金 | 从影像学看折磨伟人一生的顽疾

窗外车流不息，时光并未停歇，我们探索未知的脚步，也不会踌躇

这就是先行者们最大的贡献，也是最好的祭奠

因为霍金老爷子，让渐冻症这个罕见病走进人们的视野，

渐冻症，一起回顾一个CASE

HISTORY

A 45-year-old man presented with progressive dysphonia of 2 years duration. After the onset of dysphonia, the patient had started developing dysarthria. Several months later, he began noticing progressive motor weakness, first in the hands and then in the legs. He also noticed fasciculations involving different muscles of the extremities and trunk. These were sometimes associated with muscle aches and cramps. The patient's condition deteriorated to the point where he was unable to perform his job as a fisherman. His speech became unintelligible, and he was unable to chew solid food.

病史：

45岁男性，渔民，进行性发音困难2年。发音困难出现后，患者出现进展性构音障碍。数月后出现进行性肌无力，手部最先出现，而后累及下肢；同时，肢体及躯干不同肌肉出现肌束震颤；有时伴疼痛及痉挛。以上症状逐渐恶化以致无法再捕鱼、无法咀嚼固态食物，说话别人也难以听懂。

Physical examination showed significant atrophy and fasciculations of the tongue and bilateral mild facial weakness. However, the pupillary reflexes were normal. Examination of the limbs showed pronounced atrophy of the muscles of the forearm and of the intrinsic muscles of the hands. Similar findings were seen in the feet and legs. Motor strength was diminished. Deep tendon reflexes were brisk with clonus and a positive Babinski sign on one side.There was no vitamin B12 deficiency, and protein electrophoresis did not show an abnormal band. Further work-up included electromyography and magnetic resonance (MR) imaging of the brain.

查体：

双瞳对光反射正常；双侧面肌轻度无力；舌肌明显萎缩伴震颤；手部内侧、前臂、下肢、足部肌肉明显萎缩；四肢肌力减弱；腱反射亢进，可见肌阵挛；一侧Babinski征（+）。

辅助检查：

蛋白质电泳、VitB12浓度检查均正常。

FINDINGS

Electromyography showed denervation potentials. Unenhanced brain MR imaging demonstrated abnormally high signal intensity on both proton-density–weighted and T2-weighted images. This high signal intensity extended from the subcortical white matter of the motor cortex and the corona radiata (Fig 1), through the most posterior aspect of the internal capsule (Fig 2), and into the cerebral peduncles (Fig 3).The abnormality appeared symmetric and well-circumscribed. Coronal MR imaging demonstrated continuous linear involvement (Fig 4). Low signal intensity was seen along the precentral gyrus on T2-weighted images (Fig 5). Both the corresponding T1-weighted images and MR images of the cervical spine demonstrated normal findings.

肌电图见失神经电位。

质子密度加权像（proton density weighted image，PdWI）和T2像均见：双侧由皮质运动区的皮质下白质及放射冠开始（图1），经内囊后肢（图2），延伸至大脑脚（图3）的高信号区，边界清楚而对称。冠状位T2像更见连续的线状异常高信号（图4）。在T2像上沿中央前回可见周围低密度区（图5）。颈椎MRI未见异常。

Figure 1. Axial T2-weighted MR image (repetition time msec/echo time msec = 2,550/90) shows the subcortical white matter fibers of the motor cortex with abnormally high signal intensity (arrows).

图1. T2像示双侧皮质运动区的皮质下白质纤维见异常高信号（箭头处）

Figure 2. Axial proton-density-weighted MR image (2,550/30) shows bilateral, well-circumscribed areas of high signal intensity involving the most posterior aspect of the posterior limb of the internal capsule (arrows).

图2. 质子密度加权像（PdWI）于双侧内囊后肢后份均见边界清楚的高信号区（箭）

Figure 3. Axial T2-weighted MR image (2,550/90) shows extension of abnormally high signal intensity into the cerebral peduncles (arrows).

图3. T2像见双侧大脑脚高信号区（箭）

Figure 4. Coronal T2-weighted MR image (2,000/80) obtained at the level of the posterior limb of the internal capsule shows continuous abnormal high signal intensity extending from the cerebral cortex through the corona radiata, internal capsule, and ventral brain stem (arrows).

图4. 冠状位T2像见由双侧大脑皮层经放射冠、内囊一直延伸至脑干腹侧的连续的异常高信号影。（箭）

Figure 5. Axial T2-weighted MR image (2,550/90) obtained at the level of the cerebral cortex shows a band of low signal intensity involving the precentral gyrus (arrows).

图5. T2像于双侧中央前回可见带状低信号影。（箭）

DIAGNOSIS: Amyotrophic lateral sclerosis.

诊断：肌萎缩侧索硬化（amyotrophic lateralizing sclerosis，ALS）

DISCUSSIONAmyotrophic lateral sclerosis, the most common form of motor neuron disease, is a devastating, progressive, neurodegenerative disorder that demonstrates both upper (hyperreflexia, spasticity) and lower (fasciculation, atrophy) neuronal symptoms. By definition, there should be no autonomic, sensory, or cognitive involvement. The El Escorial diagnostic criteria are typically used for clinical diagnosis (1). Amyotrophic lateral sclerosis demonstrates a male predilection with onset in the middle and late adult years (2).

讨论：

肌萎缩侧索硬化是运动神经元病的最常见类型，男性较女性多见，常于中年以后起病，是隐袭起病、进行性发展、兼有上（肌强直、腱反射亢进等）、下（肌束震颤、萎缩）运动神经元受累的神经变性疾病。感觉、自主神经、认知功能不受累。

临床诊断通常依据E1 Escorial诊断标准。

At gross examination, the brain may show atrophy of the precentral gyrus. At microscopic analysis, there is loss of pyramidal and Betz cells in the motor cortex with loss of anterior horn cells in the spinal cord. The proximal axons of the neuronal cells show swelling. Ferric stains demonstrate strong staining for iron (2).病理标本可见中央前回萎缩；镜下可见大脑皮质运动区锥体细胞、Betz细胞数量减少，脊髓前角细胞明显减少，邻近的轴突肿胀。铁染色呈强阳性。

The exact cause of the disease is not well known. However, after the recent discovery of a mutation in the gene encoding the enzyme superoxide mutase-1 in some patients with the disease, the theory of free radical damage to neurons would appear to be the most plausible. Other theories include an autoimmune process or heavy metal toxicity (2).具体病因不明。但超氧化物歧化酶（enzyme superoxidemutase-1，SOD1）基因突变与肌萎缩侧索硬化有关已公认，可能与自由基损伤神经元有关。其他学说还有自身免疫、重金属中毒机制等。

The primary role of imaging in amyotrophic lateral sclerosis is to exclude other causes such as cervical degenerative disk disease, Chiari malformation, or multiple sclerosis. Imaging is also helpful in atypical cases of the disease (3).对肌萎缩侧索硬化，影像学检查的主要作用是排除其他疾病，如颈椎间盘变形、Chiari's畸形、多发性硬化等。同时，对于明确导致该病的一些不典型病因也有帮助。

Fairly typical MR imaging findings have been described in patients with amyotrophic lateral sclerosis (4). High signal intensity is seen involving the corticospinal tract at both T2-weighted and proton-density–weighted imaging, with the latter being more sensitive (2). This abnormal signal intensity extends from the corona radiata, through the most caudal aspect of the posterior limb of the internal capsule, into the ventral aspect of the brain stem, and finally into the anterolateral column of the spinal cord (2,5). Involvement of the corpus callosum has also been reported (6). High signal intensity in the corticospinal tract has also been described in some healthy individuals, along with Friedreich ataxia and vitamin B12 deficiency (7). In such cases, however, the abnormal signal intensity is usually limited to the internal capsule and does not extend to the corona radiata or brain stem as in amyotrophic lateral sclerosis (2). This extended involvement distinguishes amyotrophic lateral sclerosis from the periventricular pattern of multiple sclerosis (1).肌萎缩侧索硬化典型的MRI表现是：质子密度加权像（PdWI像）和T2像均可见皮质脊髓束高信号，质子密度加权像上更明显。这种异常信号常从放射冠经内囊后肢最尾部，再经脑干腹侧部，最终延伸至脊髓前外侧柱。文献也曾报道胼胝体也可受累。

在健康人群、Friedreich共济失调、VitB12缺乏症患者，也可出现皮质脊髓束的异常高信号，但常局限于内囊，不向放射冠、脑干延伸。

同时，肌萎缩侧索硬化异常信号的延伸性特点也有助于和多发性硬化的室周异常脱髓鞘信号相鉴别。

In addition, T2-weighted MR imaging typically demonstrates low signal intensity in the motor cortex in amyotrophic lateral sclerosis. This finding has been attributed to T2 shortening due to iron deposition (3). Use of MR spectroscopy and magnetization transfer techniques for early identification of amyotrophic lateral sclerosis has also been reported (8,9). However, further research is probably needed.另外，肌萎缩侧索硬化典型影像学改变还有：T2像大脑皮质运动区的低信号影。据认为与铁沉积所致的T2缩短效应有关。也有报道，利用MRS和磁化传递技术来早期识别肌萎缩侧索硬化，但可能还需进一步深入研究。

来源 | 医学影像学英语