SECTION 1 第一部分
A 12-year-old boy presented with 3 weeks of calf pain, tripping, and progressive inability to walk. The onset was preceded by a sore throat 4 weeks prior, but no recent immunizations and no sick contacts. He began having problems “catching his toes” for 2 weeks. He had no visual complaints and no bowel or bladder incontinence. He had no recent travel and there were no heavy metal or solvent exposures. He had no prior medical history and he was on no prescription medications. Developmentally, he was on track and had just successfully completed fifth grade. However, he was reported to be behaviorally oppositional, especially regarding his diet which was restricted to beef jerky, yogurt from a squeeze tube, and fruit drinks. Family history included diabetic peripheral neuropathy in his mother, idiopathic peripheral neuropathy in his maternal grandfather, and left lower extremity neuropathy from trauma in his father. There was no known family history of recurrent pressure palsies or cardiac problems.
12岁男孩，出现小腿疼痛，跌倒，渐进性行走不能症状3周。在发病4周前出现喉咙疼痛，无近期免疫接种和疾病接触史。2周前他开始出现“抓脚趾” 问题。无视觉异常主诉，无尿便失禁。无近期外出史，无重金属或溶剂接触史。既往无特殊病史，无服药史。发育一直正常，刚读完小学五年级。但是，近期行为有些反常，特别是他的饮食仅限于牛肉干、带吸管的酸奶和果汁。家族史包括他母亲患有糖尿病周围神经病变，他祖父患有特发性周围神经病变，他父亲患有创伤性左下肢神经病变。无周期性压力性麻痹或及心脏疾病家族史。
His vital signs were normal with the exception of a body mass index of 11.1 kg/m2.His general examination showed periorbital edema and was otherwise normal including cardiac and skin examinations. Mental status examination revealed an apathetic affect with normal alertness and mentation. Cranial nerves were normal. Motor examination revealed normal strength in the upper extremities and proximal lower extremities with mild weakness on knee flexion and extension but absent ankle dorsiflexion and eversion. There was tenderness to palpation of both calves. Deep tendon reflexes were absent at the patellae and Achilles. Response to plantar stimulus was flexion bilaterally. Sensation was normal in the upper extremities but decreased to light touch, temperature, and pinprick on the dorsum of both feet to the level of the ankles. Coordination testing was normal. He was able to stand independently but was wide-based and he ambulated with a high-steppage gait bilaterally.
was preceded by a sore throat 4 weeks prior, but no recent immunizations and no sick contacts. He began having problems “catching his toes” for 2 weeks. He had no visual complaints and no bowel or bladder incontinence. He had no recent travel and there were no heavy metal or solvent exposures. He had no prior除体重指数为11.1kg/ m2外，他生命体征正常。一般检查可见眶周水肿，包括心脏和皮肤的其他检查均正常。精神状态检查提示对正常的警觉性和心理状态反应淡漠。颅神经检查正常。运动系统检查发现上肢和下肢近端肌力正常，膝关节屈伸力量轻度减弱，但没有踝关节背屈、外翻。双侧小腿触痛。膝腱反射和跟腱反射消失。双侧跖反射屈曲。双上肢感觉正常但双足背到踝关节水平针刺觉、轻触觉，温觉均减退。共济检查正常。他可以独自站立但步基增宽，行走时双下肢呈跨阈步态。
Question for consideration:
1. What is the differential diagnosis for ascending weakness in a child?
考虑的问题：
1、该患儿上行性无力的鉴别诊断是什么？
SECTION 2 第二部分
Progressive, symmetric, ascending weakness in children has a broad differential that typically includes neoplastic (spinal compression), autoimmune, such as acute inflammatory demyelinating polyradiculoneuropathy (AIDP), infectious, spinal cord lesions, toxic exposure such as heavy metal poisoning, and nutritional deficiencies. Spinal compression syndromes can present with symmetric or asymmetric lower extremity weakness and sensory loss. Diminished deep tendon reflexes, urinary retention, and poor rectal tone are typical. AIDP classically presents with symmetric ascending weakness and should always be suspected in this setting. Absence of reflexes and sensory changes are common. Infectious etiologies such as HIV, enterovirus, and West Nile virus can cause subacute progressive weakness. Enterovirus and West Nile viral infections can cause acute flaccid paralysis similar to poliomyelitis. However, enteroviral radiculomyelitis tends to be unilateral and painful. Flaccid paralysis from West Nile virus is also more commonly asymmetric and is often associated with encephalitis or meningitis. Transverse myelitis and other myelopathies can cause progressive ascending weakness, but can often be differentiated from neuropathy by physical examination and a history of back pain. The usual presenting feature of transverse myelitis is sudden onset of combined motor and sensory disturbance in the trunk and legs. Sphincter dysfunction is common and there is often a sensory level to pain and temperature that indicates the level of the lesion. Deep tendon reflexes below the lesion may be initially depressed and then become hyperactive. Motor symptoms are seldom the sole complaint of toxic or metabolic neuropathies. The list of potentially offending medications is long and the most common medications that could produce neuropathy include chemotherapeutics (vincristine), cardiovascular drugs (amiodarone), immunosuppressives (colchicine), and antimicrobials (nitrofurantoin). Heavy metal toxicity is rare and the neuropathy is usually associated with gastrointestinal, hematologic, and CNS dysfunction. Nutritional deficiencies can cause myelopathy and neuropathy, but are less common in developed countries with routinely fortified foods. Sensory abnormalities, without a sensory level, are common in vitamin deficiency neuropathies.
儿童出现进展性，对称性，上升性无力的鉴别诊断有很多，通常包括neoplastic (spinal compression), autoimmune, such as acute inflammatory demyelinating polyradiculoneuropathy (AIDP), infectious, spinal cord lesions, toxic exposure such as heavy metal poisoning, and nutritional deficiencies.肿瘤（脊髓压迫）、自身免疫性疾病，如急性炎症性脱髓鞘性多发性神经病（AIDP）、感染、脊髓病变、毒物如重金属中毒和营养不良。脊髓压迫综合征可伴有对称或不对称的下肢无力和感觉丧失。典型表现为腱反射消失，尿潴留和直肠功能减弱。AIDP的典型表现为对称的上升性无力，当出现该症状时应高度怀疑此病。反射和感觉缺失也很常见。感染性病因如HIV、肠道病毒和西尼罗河病毒可导致亚急性进展性肌无力。肠道病毒和西尼罗河病毒感染可引起急性弛缓性麻痹，类似脊髓灰质炎。然而，肠道病毒引起的脊髓炎往往单侧发病合并有疼痛。西尼罗河病毒引起的弛缓性麻痹多不对称，并经常引起脑炎或脑膜炎。横贯性脊髓炎和其他脊髓病可引起进行性上升性无力，但往往通过神经系统体格检查和背部疼痛病史可以鉴别。横贯性脊髓炎通常表现是突然起病的躯干和下肢的运动和感觉障碍。括约肌功能障碍常见，往往有一个可以提示病变的水平的痛温觉感觉平面。在病变以下深腱反射最初会减弱，然后会变得亢进。中毒或代谢性神经病变的运动症状很少作为唯一的主诉。可能引起神经病变的药物很多，最常见的药物include chemotherapeutics (vincristine), cardiovascular drugs (amiodarone), immunosuppressives (colchicine), and antimicrobials (nitrofurantoin).包括化疗药（长春新碱）、心血管药物（胺碘酮）、免疫抑制剂（秋水仙素）和抗菌药物（呋喃妥因）。重金属中毒罕见，引起的神经病变通常与胃肠道、血液系统和中枢神经系统的功能障碍有关。营养缺乏可导致脊髓病和神经病变，但在常规应用强化食品的发达国家并不常见。没有感觉平面的感觉异常在维生素缺乏导致的神经病变中常见。
Question for consideration:
1. What tests would you order?
需要考虑的问题：
1、你会对他做什么检查？
SECTION 3 第三部分
The patient underwent spinal MRI with and without gadolinium. There was no spinal nerve root enhancement or other explanation of his clinical presentation. A lumbar puncture was acellular with normal protein and glucose and was negative for West Nile virus immunoglobulin G and immunoglobulin M antibodies.
给予患者行脊髓MRI以及钆增强脊髓MRI。无脊神经根增强，无其他可以解释其临床表现的结果。腰椎穿刺脑脊液中无细胞，蛋白和葡萄糖正常，西尼罗河病毒免疫球蛋白G和免疫球蛋白M抗体阴性。
Two days later, he became lethargic and was noted to have a bounding heart rate and a new S3 heart sound on auscultation. He was subsequently transferred to the pediatric intensive care unit where an urgent transthoracic echocardiogram demonstrated normal systolic function but a small pericardial effusion. Brain natriuretic peptide was markedly elevated at 2,189 pg/mL (0–100), troponin I was elevated at 0.18 ng/mL (0.00–0.04), and he was started on milrinone infusion. He remained hemodynamically stable and did not require intubation.
两天后，他出现昏睡，心率增快，听诊发现S3心音。随后他被转移到儿科ICU，给予紧急经胸超声心动图检查显示收缩功能正常，但少量心包积液。脑钠尿肽显著升高至2189 pg/ml（正常值0–100），肌钙蛋白 I 升高至0.18 ng/mL（正常值0–0.04），开始给他泵入米力农。他血流动力学尚稳定无需插管。
Electrodiagnostic testing revealed distal predominant sensorimotor axonal peripheral neuropathy. On nerve conduction, bilateral superficial peroneal sensory nerve responses were absent, the left peroneal motor response was absent, and the right was markedly reduced in amplitude to 0.7 mV (normal .3 mV). F-wave responses were absent in the bilateral peroneal motor nerves but normal in the upper extremities. Needle EMG revealed evidence of acute denervation as well as reinnervation. There was evidence of both acute and chronic denervation including diffuse fibrillations as well as morphologically large and complex rapid firing motor units in the right tibialis anterior, vastus lateralis, and gastrocnemius.
电生理测定提示为远端为主的感觉运动性轴索型周围神经病变。在神经传导方面，双侧腓浅神经浅感觉缺失，左腓总神经运动觉缺失，右侧波幅为0.7mv，较正常显著降低（正常3mv）。双侧腓总神经运动神经F波缺失，但双上肢正常。针极肌电图显示急性神经损伤以及失神经支配的证据。急性和慢性失神经支配的证据包括在右胫骨前肌、股外侧肌和腓肠肌出现的弥漫性纤颤电位以及形态大而复杂的快速放电运动单位电位。
Questions for consideration:
1. Does this information change the differential diagnosis?
2. What further investigations would you order?
需要考虑的问题：
1、 以上资料会不会改变鉴别诊断？
2、你还需要进一步做什么检查？
SECTION 4 第四部分
The differential diagnosis for ascending motor neuropathy and heart failure in the pediatric population is limited and consists of AIDP and vitamin deficiency. Acute heart failure in the setting of AIDP has been reported. The mechanism is neurogenically stunned myocardium as is seen with Takotsubo cardiomyopathy from sympathetic overactivation in the setting of inflammatory disease. Another known cause of peripheral neuropathy and heart failure is nutritional deficiency of vitamin B1. Classic terminology has categorized the clinical manifestations of thiamine deficiency into dry beriberi, characterized by sensorimotor neuropathy of the lower extremities, and wet beriberi, characterized by edema and heart failure. Acute presentation of wet beriberi results in rapid cardiac deterioration whereas the chronic form results in high-output heart failure and hypertension. Dry beriberi is chronic and results in symmetric, ascending paralysis with calf pain and absent deep tendon reflexes. It is not currently evident why certain people exhibit different forms of thiamine deficiency. Our patient developed both neurologic and cardiac problems associated with thiamine deficiency. Most cases of pediatric thiamine deficiency have been reported as Wernicke encephalopathy. The reason thiamine deficiency can present so heterogeneously is unknown and it is unclear why most cases of pediatric thiamine deficiency present as an encephalopathy.
儿童人群中出现上升性运动神经病变和心力衰竭的鉴别诊断很有限，包括AIDP和维生素缺乏。AIDP发生急性心力衰竭已有报道。其机制是心肌神经源性顿抑，就像在炎性疾病时，交感神经的过度激活导致Takotsubo心肌病。另一个导致的外周神经病变和心脏衰竭已知的原因是维生素B1的缺乏。经典术语将硫胺素缺乏症的临床表现分类为以下肢感觉运动性神经病变为特征的干性脚气病，和以水肿和心力衰竭为特征的湿性脚气病。湿性脚气病急性期可导致心脏功能快速恶化，而慢性型则导致高输出量型心力衰竭和高血压。干性脚气病是慢性的，导致出现双小腿对称性、进展性麻痹伴疼痛，深部腱反射消失。目前还不清楚为何不同人群会表现出不同形式的硫胺素缺乏症。该患者出现了硫胺素缺乏相关的神经系统障碍和心脏疾患。儿童维生素B1缺乏症大多数情况下以Wernicke脑病被报道。硫胺素缺乏能够表现出不同类型的原因不明，目前还不清楚为什么多数情况下儿童硫胺素缺乏表现为脑病。
In this patient, serum vitamin B1 was 2 mol/mL(8–30) (table). With the history of severely restricted diet and low thiamine, a diagnosis of thiamine deficiency was made. He was started on 100 mg IV thiamine once followed by IV treatment of 25 mg daily. The electrodiagnostic findings supported his diagnosis via a distal-predominant axonal polyneuropathy affecting both motor and sensory nerves.
该患者血清维生素B1是2mol/ml（正常值为8 - 30）（表）。结合该患者严重限制饮食的病史和低维生素B1水平，确立维生素B1缺乏症的诊断。给予首次静点100mg维生素B1治疗后，随后给予每天静点维生素B1 25mg。电生理检查结果发现远端为主的双侧运动和感觉神经异常的轴索型多神经病变，支持该诊断。
表 血清学检验结果
实验室检查
结果
叶酸、维生素B12, MMA
正常
维生素A, B6, E
正常
CBC
血红蛋白11.6 g/dL (正常值13–16)
铜、锌
正常
CPK, TSH
正常
TTG, RBP
阴性
ESR, CRP, 铁蛋白
正常
缩写：CBC=全血细胞计数；CPK=肌酸磷酸激酶；CRP=C反应蛋白;；ESR =红细胞沉降率；Hgb=血红蛋白；MMA=甲基丙二酸；RBP=视黄醇结合蛋白；TSH=促甲状腺激素；TTG=谷氨酰胺转胺酶。
Whole blood thiamine is a good laboratory indicator of body stores of thiamine whereas plasma thiamine concentration is more indicative of recent thiamine intake and can be transiently decreased as part of an acute inflammatory response, especially in critically ill patients. Similar to plasma thiamine, red blood cell transketolase activity is sensitive to thiamine replacement and will normalize within a few hours after thiamine treatment. The persistent restricted eating pattern was likely behaviorally mediated, as he had no medical (gastroesophageal reflux), anatomical (cleft palate, microgastria), or developmental disabilities to explain the problem with food refusal. The behavior seemed to have begun during the toddler years, but rather than resolve as expected, it developed into a chronic restricted pattern.
全血硫胺素是判断机体硫胺素贮存的一个很好的实验室指标，而血浆硫胺素浓度更能提示近期硫胺素摄入，尤其是在危重病人中，血浆硫胺素浓度会因急性炎症反应短暂性下降。和血浆硫胺素相似，红细胞转酮醇酶活性对于硫胺素替代治疗敏感，并会在治疗数小时后使之恢复正常。如他没有疾病（胃食管反流），解剖异常（腭裂，小胃畸形），或发育性畸形来解释厌食问题，那持续饮食限制可能是节食引起的，这种行为似乎在幼儿时期就已经开始了，但并没有去解决，而是发展成一种长期节食状态。
Questions for consideration:
1. Is there a genetic predisposition toward developing beriberi from thiamine deficiency?
2. How would you manage this patient?
需要考虑的问题：
1. 从硫胺素缺乏到发展为脚气病是否有遗传倾向？
2. 你怎样治疗该患者？
SECTION 5 第五部分
Some literature suggests a genetic sensitivity toward a lower threshold of developing clinical manifestations in the setting of low thiamine. Whether a patient will develop either neurologic or cardiac manifestations may be due to an underlying genetic predisposition.
一些文献表明，对低硫胺素血症患者出现临床表现的阈值更低，这种情况具有遗传易感性。无论病人会发展为神经系统或心脏的表现可能都是由于潜在的遗传易感性。
Children with comorbidities including neuropsychiatric disorders such as depression and eating disorders are at risk of poor diet leading to potential vitamin deficiency. In thiamine deficiency, initial replacement with 100 mg IV thiamine followed by daily administration of 25–50 mg is necessary to avoid further progression of neuropathy or cardiomyopathy. Repeat serum and whole blood thiamine are useful to monitor recent thiamine intake and overall thiamine body stores, respectively. Physical rehabilitation is necessary in severe cases of neuropathy or cardiac involvement. Management of children with continued food refusal requires psychological and behavioral management as well as caregiver training. Due to poor oral intake, a nasal feeding tube is often required for nutrition. Follow-up electrodiagnostic testing may be valuable for assessment of peripheral nerve improvement.
合并有神经精神疾病如抑郁症和饮食失调症的儿童，有营养不良导致潜在维生素缺乏的风险。硫胺素缺乏症患者，为了避免进一步进展的神经病变或心肌病，首次给予100mg硫胺素静点，然后每日给予25-50mg静点是必要的。重复血清和全血硫胺素检查对分别监测近期硫胺素摄入量和机体硫胺素储备是有帮助的。物理疗法对神经病变或心脏受累的重症患者很必要。持续厌食的儿童需要对其进行心理和行为管理以及护理者对其培训。由于口服摄入不足，需经常通过鼻饲管补充营养。后续的电生理检测对于周围神经功能改善的评估可能会有价值。
The patient was lost to neurologic follow-up.
最后该患者失访。
（全文终）
诗句赏析
The supreme happiness of life is the conviction that we are loved. —Victor Hugo
生活中最大的幸福是坚信有人爱我们。—维克多·雨果
编辑：李会琪
：
【招聘】李神经群招募英语文献翻译及审校人员的公告
