Rubboli Guido, Veggiotti Pierangelo, Pini Antonella, Berardinelli Angela, Cantalupo Gaetano, Bertini Enrico, Tiziano Francesco Danilo, D'Amico Adele, Piazza Elena, Abiusi Emanuela, Fiori Stefania, Pasini Elena, Darra Francesca, Gobbi Giuseppe, Michelucci Roberto
Danish Epilepsy Center, Filadelfia/University of Copenhagen, Dianalund, Denmark.
Neurology Unit, Bellaria Hospital, IRCCS Institute of Neurological Sciences, Bologna, Italy.
Epilepsia. 2015 May;56(5):692-8. doi: 10.1111/epi.12977. Epub 2015 Apr 3.
To present the clinical features and the results of laboratory investigations in three patients with spinal muscular atrophy associated with progressive myoclonic epilepsy (SMA-PME), a rare condition caused by mutations in the N-acylsphingosine amidohydrosilase 1 (ASAH1) gene.
The patients were submitted to clinical evaluation, neurophysiologic investigations (that included wakefulness and sleep electroencephalography [EEG], video-polygraphic recording with jerk-locked back-averaging, multimodal evoked potentials, and electromyography), brain magnetic resonance imaging (MRI), biochemical screening, muscle and skin biopsies, and molecular genetic analysis.
The main clinical features were onset in childhood with proximal muscular weakness, generalized epilepsy with absences and myoclonic seizures, cognitive impairment of variable degree; the course was progressive with muscle wasting and uncontrolled epileptic seizures. In one patient, earlier onset before the age of 2 years was associated with a more complex clinical picture, with abnormal eye movements, progressive cognitive impairment, and a more rapid and severe course. EEG/polygraphic data were consistent with PME, demonstrating generalized spike-and-wave discharges, evidence of positive and negative myoclonia, and prominent photosensitivity. In one patient, transcranial magnetic stimulation showed a hyperexcitable motor cortex, whereas somatosensory evoked potentials were unaffected. Possible involvement of the central acoustic and visual pathways was suggested by abnormal auditory and visual evoked potentials. Muscle biopsies showed typical signs of neurogenic damage. Molecular genetic analysis showed mutations of the ASAH1 gene.
Our data indicate that SMA-PME associated with ASAH1 mutations is a genetically distinct condition with specific clinical and neurophysiologic features. Further studies are warranted to explore the role of the ASAH1 gene in muscle and brain function.
介绍3例脊髓性肌萎缩症合并进行性肌阵挛癫痫（SMA-PME）患者的临床特征及实验室检查结果，这是一种由N-酰基鞘氨醇酰胺水解酶1（ASAH1）基因突变引起的罕见病症。
对患者进行临床评估、神经生理学检查（包括清醒和睡眠脑电图[EEG]、伴有抽搐锁定反向平均的视频多导记录、多模态诱发电位和肌电图）、脑磁共振成像（MRI）、生化筛查、肌肉和皮肤活检以及分子遗传学分析。
主要临床特征为儿童期起病，近端肌无力，伴有失神和肌阵挛发作的全身性癫痫，程度不等的认知障碍；病程呈进行性，伴有肌肉萎缩和癫痫发作失控。在1例患者中，2岁前更早发病与更复杂的临床表现相关，包括异常眼动、进行性认知障碍以及更快速和严重的病程。EEG/多导记录数据与进行性肌阵挛癫痫一致，显示全身性棘慢波放电、正负肌阵挛的证据以及明显的光敏性。在1例患者中，经颅磁刺激显示运动皮层兴奋性增高，而体感诱发电位未受影响。听觉和视觉诱发电位异常提示中枢听觉和视觉通路可能受累。肌肉活检显示典型的神经源性损伤体征。分子遗传学分析显示ASAH1基因突变。
我们的数据表明，与ASAH1基因突变相关的SMA-PME是一种具有特定临床和神经生理学特征的基因独特病症。有必要进一步研究以探索ASAH1基因在肌肉和脑功能中的作用。
