Geevasinga N, Menon P, Sue C M, Kumar K R, Ng K, Yiannikas C, Kiernan M C, Vucic S
Westmead Clinical School, University of Sydney, Sydney, NSW, Australia.
Eur J Neurol. 2015 May;22(5):826-31, e57-8. doi: 10.1111/ene.12669. Epub 2015 Feb 12.
Cortical hyperexcitability has been identified as an important pathogenic mechanism in motor neuron disease (MND). The issue as to whether cortical hyperexcitability is a common process across the MND phenotypes, including amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS), remains unresolved. Separately, the clinical distinction between PLS and 'mimic disorders' such as hereditary spastic paraparesis (HSP) may be difficult, potentially delaying diagnosis. Consequently, the aim of the present study was to determine the nature and spectrum of cortical excitability changes across the MND phenotypes, and to determine whether the presence of cortical dysfunction distinguishes PLS from HSP.
Cortical excitability studies were undertaken on a cohort of 14 PLS, 82 ALS and 13 HSP patients with mutations in the spastin gene.
Cortical hyperexcitability, as heralded by reduction of short interval intracortical inhibition (PLS 0.26%, -3.8% to 1.4%; ALS -0.15%, -3.6% to 7.0%; P < 0.01) and cortical silent period duration (CSPPLS 172.2 ± 5.4 ms; CSPALS 178.1 ± 5.1 ms; P < 0.001), along with an increase in intracortical facilitation was evident in ALS and PLS phenotypes, although appeared more frequently in ALS. Inexcitability of the motor cortex was more frequent in PLS (PLS 71%, ALS 24%, P < 0.0001). Cortical excitability was preserved in HSP.
Cortical dysfunction appears to be an intrinsic process across the MND phenotypes, with cortical inexcitability predominating in PLS and cortical hyperexcitability predominating in ALS. Importantly, cortical excitability was preserved in HSP, thereby suggesting that the presence of cortical dysfunction could help differentiate PLS from HSP in a clinical setting.
皮质兴奋性过高已被确认为运动神经元病（MND）的一种重要致病机制。皮质兴奋性过高是否是包括肌萎缩侧索硬化症（ALS）和原发性侧索硬化症（PLS）在内的MND各表型的共同过程，这一问题仍未得到解决。另外，PLS与诸如遗传性痉挛性截瘫（HSP）等“模仿性疾病”之间的临床鉴别可能存在困难，这有可能延误诊断。因此，本研究的目的是确定MND各表型中皮质兴奋性变化的性质和范围，并确定皮质功能障碍的存在是否能将PLS与HSP区分开来。
对14例PLS、82例ALS以及13例伴有痉挛蛋白基因突变的HSP患者进行了皮质兴奋性研究。
短间隔皮质内抑制减少（PLS为0.26%，-3.8%至1.4%；ALS为-0.15%，-3.6%至7.0%；P<0.01）以及皮质静息期持续时间缩短（PLS的皮质静息期为172.2±5.4毫秒；ALS的皮质静息期为178.1±5.1毫秒；P<0.001）预示着皮质兴奋性过高，同时皮质内易化增加在ALS和PLS表型中很明显，尽管在ALS中更常见。运动皮质的兴奋性缺失在PLS中更常见（PLS为71%，ALS为24%，P<0.0001）。HSP患者的皮质兴奋性保持正常。
皮质功能障碍似乎是MND各表型的内在过程，皮质兴奋性缺失在PLS中占主导，而皮质兴奋性过高在ALS中占主导。重要的是，HSP患者的皮质兴奋性保持正常，因此表明在临床环境中皮质功能障碍的存在有助于将PLS与HSP区分开来。
