甲硝唑脑病易误诊为多发性硬化症
圣迭戈(EGMN)——美国西奈山医学院的Corey McGraw博士在第四届多发性硬化症合作会议上报告，对于正在使用抗生素的可疑多发性硬化症(MS)患者，应考虑到甲硝唑诱发性脑病(MIE)的可能性。
McGraw博士介绍了他遇到的1例患者：这名30多岁的克罗恩病患者已服用甲硝唑近7年，并在1年前被诊断为MS，但McGraw博士最终确定他所患的并非MS而是MIE。
该患者从2004年初曾服用甲硝唑500 mg，3次/d，持续服用数月，2005年中又以同样方式服用了甲硝唑。大约1个月后，他首次出现神经系统症状——原发性步态共济失调和构音障碍，非增强磁共振成像T2高信号。尽管如此，他仍然继续服用甲硝唑250 mg，2次/d~500 mg，3次/d，直至2011年初，在此期间又出现了多次神经症状发作，尤其是在甲硝唑剂量增加后更常出现。该患者已累计服用甲硝唑2,133.5 g。停用甲硝唑41天之后，共济失调和构音障碍几乎完全消失；7个月后，脑磁共振成像仅遗留小的高信号灶，唯一剩余的主诉为记忆力、注意力和积极性不佳。
McGraw博士还对文献中的63例病例报告进行了综述，发现44例(70%)磁共振成像显示小脑齿状核T2高信号，与本例患者一致。还有19例(30%)为胼胝体压部T2高信号。这些都是“中毒性脑病的典型表现”。构音障碍、步态共济失调、心理状态问题、手臂协调问题、腿部力量问题和癫痫也较常见。值得注意的是，本例合并克罗恩病的MIE患者每次发作都表现出同样的症状和体征，而MS的症状和体征则有在全身游走的倾向。这63例患者服用甲硝唑的平均累计剂量为106.1克(范围：3~1,095 g)，从首次服药至首次神经症状发作的平均间隔时间为67天(范围：2~730天)。症状平均在停用甲硝唑1~420天之后消失。
McGraw博士指出： “神经科医生在鉴别诊断脱髓鞘性疾病时应警惕MIE的可能，尤其是考虑到其潜在的可逆性。众所周知，甲硝唑可引起外周神经病变，但鲜为人知的是它也可引起类似脱髓鞘疾病的中毒性脑病。MIE在美国是一种尚未被充分认识的神经系统疾病。在现有的63例报告中，多数来自韩国和印度。一些非常资深的同行此前甚至从未听说过MIE，加之MIE在发作时间和累计剂量方面具有很强的可变性，因此该病很容易被漏诊或误诊。”
本次会议由多发性硬化症中心联合会和美洲多发性硬化症治疗与研究委员会共同主办。McGraw博士报告称无相关利益冲突。
爱思唯尔 版权所有
BY M. ALEXANDER OTTO
Elsevier Global Medical News
Breaking News
SAN DIEGO (EGMN) – Metronidazole-induced encephalopathy should be considered when patients on the antibiotic are worked up for suspected multiple sclerosis, according to a case study and literature review from researchers at the Mount Sinai School of Medicine in New York.
A Crohn’s disease patient in his mid-30s who had been on metronidazole for almost 7 years presented there with a years-long diagnosis of multiple sclerosis, but MS wasn’t his problem. Doctors at the center figured out he had metronidazole-induced encephalopathy (MIE).
He had been started on 500 mg three times daily for a few months in early 2004, and then restarted on the same regimen in mid-2005. His first neurologic attack – primarily gait ataxia and dysarthria, along with nonenhancing T2 hyperintensities on MRI – came about a month later. Nonetheless, he remained on 250 mg twice daily to 500 mg three times daily until early 2011, and suffered several more attacks, notably after dosage increases. His cumulative metronidazole dose was 2,133.5 g.
Forty-one days after the patient stopped taking metronidazole, his ataxia and dysarthria were almost completely resolved; 7 months later, he was almost clear on brain MRI, with only small residua. His sole remaining complaints were poor memory, attention, and motivation.
“Neurologists should be alert to the possibility of metronidazole-induced encephalopathy in the differential diagnosis of demyelinating disease, especially in view of its potential reversibility,” said lead investigator Dr. Corey McGraw, a neurologist at the school’s Corinne Goldsmith Dickinson Center for Multiple Sclerosis.
It’s widely known that metronidazole can cause peripheral neuropathy, but it is much less known that it can also cause toxic encephalopathy that mimics demyelination, he said at the Fourth Cooperative Meeting on Multiple Sclerosis.
“This is an under-recognized neurologic disease among American neurologists. Most of the [63 reported] cases have been in Korea and India, where it may be more recognized. I and my much-more-senior colleagues had never heard of metronidazole-induced encephalopathy before this case. Neurologists are probably missing it,” Dr. McGraw said.
The giveaway in the Crohn’s patient’s case was that he had the same signs and symptoms with each attack, whereas MS tends to migrate around the body.
In many ways, he was a typical MIE patient.
Of the 63 cases reviewed by Dr. McGraw, 44 (70%) had MRI T2 hyperintensities of the cerebellar dentate nuclei that were the same as those found in the Crohn’s disease patient, and 19 (30%) had T2 hyperintensities of the corpus callosum splenium. Those and other MIE findings are “classic for a toxic encephalopathy,” he said at the meeting, which was sponsored by the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
Dysarthria and gait ataxia are common, too, as well as problems with mentation, arm coordination, leg strength, and seizures.
The cumulative mean metronidazole dose in the 63 cases was 106.1 g (range, 3-1,095 g). The mean time from first dose to first neurologic attack was 67 days (range, 2-730 days). Symptoms resolved in anywhere from 1 to 420 days after metronidazole was stopped.
The “wide ranges in time to clinical manifestations and total cumulative doses may obscure the appropriate diagnosis,” Dr. McGraw noted.
Dr. McGraw said that he had no relevant disclosures.
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