Dichgans M, Herzog J, Freilinger T, Wilke M, Auer D P
Department of Neurology, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany.
Neurology. 2005 Feb 22;64(4):608-13. doi: 10.1212/01.WNL.0000151855.98318.50.
About 20% of patients with familial hemiplegic migraine (FHM) develop progressive cerebellar signs. Genetic studies have established an association with mutations in the CACNA1A gene. However, the mechanisms underlying cerebellar involvement are largely unknown.
To use proton MR spectroscopy (1H-MRS) to investigate metabolic alterations in the cerebellum as well as cortical regions known to be involved in the propagation of migraine aura.
Fifteen CACNA1A mutation carriers from three FHM families and 17 healthy control subjects were studied. Eleven patients had clinical signs of cerebellar involvement. LCModel fits were used to estimate absolute concentrations of N-acetyl aspartate (NAA), myo-inositol (mI), glutamate (Glu), choline-containing compounds, total creatine, and lactate in the superior cerebellar vermis (SCV), parietal cortex, and occipital cortex. To control for atrophy effects, automated image segmentation was performed using SPM99. The brain parenchyma fraction (BPF) was determined for all three regions.
Compared with controls, the brain parenchyma fraction (BPF), NAA, and Glu were significantly reduced and mI was significantly elevated in the SCV of patients with FHM. In contrast, no metabolite alterations were found in supratentorial regions. BPF and NAA in the SCV significantly correlated with cerebellar scores, in particular, gait ataxia.
The findings suggest that there is a regionally distinct neuronal impairment in the superior cerebellar vermis that exceeds macroscopic tissue loss. Correlations with clinical scores emphasize the functional relevance of localized atrophy (brain parenchyma fraction) and N-acetyl aspartate levels. These measures may be useful to monitor disease progression. The observed reduction in glutamate may in part reflect impaired glutamatergic neurotransmission.
约20%的家族性偏瘫性偏头痛（FHM）患者会出现进行性小脑体征。基因研究已证实其与CACNA1A基因突变有关。然而，小脑受累的潜在机制在很大程度上尚不清楚。
使用质子磁共振波谱（1H-MRS）研究小脑以及已知参与偏头痛先兆传播的皮质区域的代谢改变。
对来自三个FHM家族的15名CACNA1A突变携带者和17名健康对照者进行了研究。11名患者有小脑受累的临床体征。使用LCModel拟合估计小脑上蚓部（SCV）、顶叶皮质和枕叶皮质中N-乙酰天门冬氨酸（NAA）、肌醇（mI）、谷氨酸（Glu）、含胆碱化合物、总肌酸和乳酸的绝对浓度。为控制萎缩效应，使用SPM99进行自动图像分割。测定了所有三个区域的脑实质分数（BPF）。
与对照组相比，FHM患者的SCV中脑实质分数（BPF）、NAA和Glu显著降低，mI显著升高。相比之下，幕上区域未发现代谢物改变。SCV中的BPF和NAA与小脑评分显著相关，尤其是步态共济失调。
研究结果表明，小脑上蚓部存在区域特异性神经元损伤，其程度超过宏观组织损失。与临床评分的相关性强调了局部萎缩（脑实质分数）和N-乙酰天门冬氨酸水平的功能相关性。这些指标可能有助于监测疾病进展。观察到的谷氨酸减少可能部分反映了谷氨酸能神经传递受损。
