Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan
J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1189-1194. doi: 10.1136/jnnp-2020-324026. Epub 2020 Sep 15.
The 'split hand' sign refers to preferential wasting of the thenar and first dorsal interosseous muscles with relatively sparing of the hypothenar muscles in amyotrophic lateral sclerosis (ALS) and both cortical and spinal/peripheral excitotoxic mechanisms have been proposed. We aimed to study split hand and axonal excitability in spinal and bulbar muscular atrophy (SBMA) in which cortical motor neurons are intact.
In 35 patients with genetically confirmed SBMA, 55 with ALS, 158 with other neuromuscular diseases and 90 normal controls; split hand was strictly determined by amplitudes of compound muscle action potentials. Nerve excitability testing of median motor axons was performed in 35 SBMA and 55 patients with ALS and 45 normal controls.
Split hand was as frequently found for patients with SBMA (57%) and ALS (62%), compared with disease (20%) and normal (0%) controls. Excitability testing showed that in both SBMA and ALS, strength-duration time constant was longer, and threshold changes in depolarising threshold electrotonus and superexcitability in the recovery cycle were greater than in normal controls (p<0.01).
Split hand is not specific to ALS and can be caused by the peripheral mechanism alone in SBMA, whereas the effect of upper motor neuron lesion cannot be excluded in ALS. Our results also suggest that SBMA and ALS share common axonal excitability changes; increased nodal persistent sodium and reduced potassium currents that may accelerate motor neuronal death and differently affect axons-innervating different muscles. Ion channel modulators could be a therapeutic option for both SBMA and ALS.
“手部分离”征是指在肌萎缩侧索硬化症（ALS）中，大鱼际和第一背侧骨间肌优先萎缩，而小鱼际肌相对保留，这与皮质和脊髓/周围兴奋性毒性机制有关。我们旨在研究皮质运动神经元完好的脊髓性和延髓性肌肉萎缩症（SBMA）中的手部分离和轴突兴奋性。
在 35 名经基因证实的 SBMA 患者、55 名 ALS 患者、158 名其他神经肌肉疾病患者和 90 名正常对照者中；通过复合肌肉动作电位的振幅严格确定手部分离。对 35 名 SBMA 患者、55 名 ALS 患者和 45 名正常对照者进行正中运动神经轴突的神经兴奋性测试。
与疾病（20%）和正常（0%）对照组相比，SBMA（57%）和 ALS（62%）患者的手部分离更为常见。兴奋性测试显示，在 SBMA 和 ALS 中，强度-时间常数更长，去极化阈电紧张和超兴奋性在恢复周期中的阈值变化大于正常对照组（p<0.01）。
手部分离并非 ALS 所特有，在 SBMA 中仅由周围机制引起，而 ALS 中的上运动神经元损伤的影响不能排除。我们的结果还表明，SBMA 和 ALS 具有共同的轴突兴奋性变化；增加的节段性持续钠电流和减少的钾电流可能加速运动神经元死亡，并以不同的方式影响支配不同肌肉的轴突。离子通道调节剂可能是 SBMA 和 ALS 的一种治疗选择。
