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【Brain】成年起病的亚历山大病
Adult-onset Alexander disease: a series of eleven unrelated cases with review of the literature
Davide Pareyson1, Roberto Fancellu1, Caterina Mariotti1, Silvia Romano2, Andrea Salmaggi3, Francesco Carella4, Floriano Girotti5, Grazietta Gattellaro6, Maria Rita Carriero7, Laura Farina6, Isabella Ceccherini8 and Mario Savoiardo6
1Biochemistry and Genetics Unit, IRCCS Foundation, C. Besta Neurological Institute, Milan, 2Department of Neurology and Centre for Experimental Neurological Therapy, S. Andrea Hospital, University of Rome, Rome, 3Neurooncology Unit, 4Movement Disorders Unit, 5Neuropathology Unit, 6Neuroradiology Unit, 7Cerebrovascular Diseases Unit, IRCCS Foundation, C. Besta Neurological Institute, Milan and 8Laboratory of Molecular Genetics, G. Gaslini Institute, Genoa, Italy
Correspondence to: Davide Pareyson, MD, Biochemistry and Genetics Unit, IRCCS Foundation, C. Besta Neurological Institute, Via Celoria 11, 20133 Milan, Italy E-mail: dpareys@istituto-besta.it
Alexander disease (AD) in its typical form is an infantile lethal leucodystrophy, characterized pathologically by Rosenthal fibre accumulation. Following the identification of glial fibrillary acidic protein (GFAP) gene as the causative gene, cases of adult-onset AD (AOAD) are being described with increasing frequency. AOAD has a different clinical and neuroradiological presentation with respect to early-onset AD, as abnormalities are mainly concentrated in the brainstem–spinal cord junction. We report detailed clinical and genetic data of 11 cases of AOAD, observed over a 4-year period, and a review of the previously reported 25 cases of genetically confirmed AOAD. In our series, onset occurred as late as age 62, and up to 71 in an affected deceased relative. Most cases appeared sporadic, but family history may be misleading. The most frequent symptoms were related to bulbar dysfunction—with dysarthria, dysphagia, dysphonia (seven patients)—, pyramidal involvement (seven patients) and cerebellar ataxia (seven patients). Four patients had palatal myoclonus. Sleep disorders were also observed (four cases). Bulbar symptoms, however, were infrequent at onset and two symptomatic patients had an almost pure pyramidal involvement. Two subjects were asymptomatic. Misdiagnosis at presentation was frequent and MRI was instrumental in suggesting the correct diagnosis by showing, in all cases, mild to severe atrophy of the medulla oblongata extending caudally to the cervical spinal cord. In ten patients, molecular studies revealed six novel missense mutations and three previously reported changes in GFAP. The last typical patient carried no definitely pathogenic mutation, but a missense variant (p.D157N), supposedly a rare polymorphism. Revision of the literature and the present series indicate that the clinical picture is not specific, but AOAD must be considered in patients of any age with lower brainstem signs. When present, palatal myoclonus is strongly suggestive. Pyramidal involvement, cerebellar ataxia and urinary disturbances are common. Less frequent findings include sleep disorders and dysautonomia. Fluctuations may occur. The course is variable, usually slowly progressive and less severe than the AD forms with earlier onset. AOAD is more common than previously thought and might even be the most common form of AD. The diagnosis is strongly suggested by MRI and confirmed by GFAP gene analysis. 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 编译如有不妥之处，欢迎广大战友指正！ 成年起病的亚历山大病：11例不相关的的病例分析与文献综述
典型的亚历山大病是婴幼儿期致命性的脑白质病，病理学上以Rosenthal纤维的积聚为特征。自从确认神经胶质酸性蛋白基因为该病的起病基因，成年起病的亚历山大病被报道的频率越来越高。成年起病的亚历山大病具有与早发型亚历山大病不同的临床和神经系放射学的表现，其异常主要集中在脑干脊髓接合处。我们报道了11例成年起病的亚历山大病详细的临床和基因数据，进行了为期4年多的观察，并回顾了先前报道的25例通过遗传学证实的成年起病的亚历山大病。在我们收集的病例中，发病年龄可以晚到62岁，一直到71岁有已故的受累的亲属。大多数病例表现为散发的，家族史可能产生误导。 最常见的症状有由于延髓功能障碍导致的构音障碍、吞咽困难、发声困难（7人），锥体系受累（7人）和小脑性共济失调（7人）。四位患者有腭肌阵挛,也可观察到睡眠障碍（4人）。然而，延髓症状在发病初期并不常见，两位有症状的患者几乎完全为锥体系受累表现另外两位患者无症状。误诊在目前是常见的，在所有的病例中，通过显示延髓轻到重度的萎缩且向尾端延伸到颈段脊髓，磁共振成像可以有助于做出正确的诊断。十位患者分子水平的研究揭示神经胶质酸性蛋白有六个异常的错义突变和三个先前已报道的改变。最近的这位典型患者没有携带任何明确的可以致病的突变，但是仍具有一个错义突变 (p.D157N) ，推测为罕见的多态现象。通过回顾文献和目前病例可知，成年起病的亚历山大病的临床表现没有特异性，对于具有低位脑干体征的任何年龄患者都应考虑到成年起病的亚历山大病的可能，出现腭肌阵挛更强烈支持此诊断。常见的有锥体系受累、小脑性共济失调和排尿困难。次常见的包括睡眠障碍和家族性自主神经机能异常。可能会出现症状波动。病程多不相同，常呈缓慢进行性且没有早发型亚历山大病严重。成年起病的亚历山大病较先前的认为更为常见，而且甚至可能是亚历山大病中最常见的类型。磁共振成像可以强有力的支持诊断，而神经胶质酸性蛋白基因分析则可以确诊该病。 [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-05-28 17:14
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