Service of Neurology, Hospital Universitario Miguel Servet, Avenida Isabel la Católica, 1-3, 50009, Zaragoza, Spain.
J Neurol. 2012 May;259(5):869-78. doi: 10.1007/s00415-011-6269-5. Epub 2011 Oct 13.
The aim of the study was to enhance our understanding of the pathogenesis of the ataxia of Charlevoix-Saguenay, based on the findings presented herein. Five patients with a molecular diagnosis of this disease underwent clinical, radiological, ophthalmologic and electrophysiological examinations. Five novel mutations, which included nonsense and missense variants, were identified, with these resulting in milder phenotypes. In addition to the usual manifestations, a straight dorsal spine was found in every case, and imaging techniques showed loss of the dorsal kyphosis. Cranial MRI demonstrated hypointense linear striations at the pons. Tensor diffusion MRI sequences revealed that these striations corresponded with hyperplastic pontocerebellar fibres, and tractographic sequences showed interrupted pyramidal tracts at the pons. Ocular coherence tomography demonstrated abnormal thickness of the nerve fibre layer. Electrophysiological studies showed nerve conduction abnormalities compatible with a dysmyelinating neuropathy, with signs of chronic denervation in distal muscles. The authors suggest that the hyperplastic pontocerebellar fibres compress the pyramidal tracts at the pons, and that the amount of retinal fibres traversing the optic discs is enlarged. These facts point to the contribution of an abnormal developmental mechanism in the ataxia of Charlevoix-Saguenay. Accordingly, spasticity would be mediated by compression of the pyramidal tracts, neuromuscular symptoms by secondary axonal degeneration superimposed on the peripheral myelinopathy, while the cause of the progressive ataxia remains speculative. The distinctive aspect of the dorsal spine could be of help in the clinical diagnosis.
本研究旨在基于本文所呈现的发现，深入了解 Charlevoix-Saguenay 共济失调的发病机制。对五名经分子诊断为此病的患者进行了临床、影像学、眼科和电生理学检查。发现了五个新的突变，包括无义和错义变异，导致表型较轻。除了常见的表现外，每个病例都有直的背部脊柱，影像学技术显示背侧后凸消失。颅磁共振成像显示桥脑有低信号线性条纹。张量扩散磁共振成像序列显示这些条纹与桥脑增生性桥小脑纤维相对应，轨迹成像序列显示桥脑的锥体束中断。眼相干断层扫描显示神经纤维层厚度异常。电生理学研究显示神经传导异常符合脱髓鞘神经病，远端肌肉有慢性去神经支配的迹象。作者认为，增生性桥脑小脑纤维压迫桥脑的锥体束，穿过视盘的视网膜纤维数量增加。这些事实表明异常发育机制在 Charlevoix-Saguenay 共济失调中起作用。因此，痉挛可能是由锥体束受压引起的，神经肌肉症状是继发于周围脱髓鞘神经病的轴突变性，而进行性共济失调的原因仍有待推测。背部脊柱的独特表现有助于临床诊断。
