Department of Neurology, Mayo Clinic Arizona, 13400 East Shea Blvd, Scottsdale, AZ, 85259, USA.
Clin Auton Res. 2013 Dec;23(6):333-8. doi: 10.1007/s10286-013-0205-y. Epub 2013 Aug 8.
Alexander disease (AxD) is an astrogliopathy, resulting from a mutation in the glial fibrillary astrocytic protein gene. Different clinical subtypes have been described, including infantile, juvenile, and adult onset, based upon the age at which symptoms begin. Patients with the adult-onset form, develop a progressive, spastic paraparesis, palatal myoclonus, ataxia, and bulbar weakness. Autonomic nervous system (ANS) dysfunction has been reported as a potential manifestation of adult-onset AxD, but has not been well characterized.
We report a case of adult-onset AxD with symptomatic orthostatic hypotension (OH) and heat intolerance that underwent formal autonomic testing. In addition, a comprehensive literature search was conducted to review the frequency and pattern of autonomic dysfunction in this patient population.
A 51-year-old patient was diagnosed with AxD at the age of 47, following an 8-year history of vertigo, intermittent diplopia, and sleep disturbance. The patient developed symptoms of OH, erectile dysfunction, and heat intolerance soon after his diagnosis. Autonomic testing demonstrated OH on tilt-table testing (47 mmHg decrease in BP with 18 BPM heart rate increment) with absent late phase II and IV responses during the Valsalva maneuver, severe cardiovagal impairment, and preserved postganglionic sympathetic sudomotor function. These findings were interpreted as being consistent with central autonomic failure. The most common autonomic symptoms reported in other AxD cases include constipation, urinary incontinence, and sphincter dysfunction. To our knowledge, this is the first report of formal autonomic testing in AxD.
Signs and symptoms of ANS impairment can occur in patients with AxD, and can include orthostatic hypotension and bowel/bladder dysfunction. Autonomic testing in our patient suggests impairment in central autonomic pathways.
亚历山大病（AxD）是一种星形胶质病，由神经胶质纤维酸性蛋白基因突变引起。根据症状开始的年龄，已描述了不同的临床亚型，包括婴儿型、青少年型和成年型。成年型患者会出现进行性痉挛性截瘫、软腭肌阵挛、共济失调和球部无力。自主神经系统（ANS）功能障碍已被报道为成年型 AxD 的潜在表现，但尚未得到很好的描述。
我们报告一例成年型 AxD 伴有症状性直立性低血压（OH）和不耐热，该患者接受了正式的自主神经测试。此外，还进行了全面的文献检索，以综述该患者人群中自主神经功能障碍的频率和模式。
一名 51 岁男性患者在出现眩晕、间歇性复视和睡眠障碍 8 年后于 47 岁时被诊断为 AxD。该患者在诊断后不久即出现 OH、勃起功能障碍和不耐热的症状。倾斜试验显示 OH（BP 下降 47mmHg，心率增加 18 BPM），瓦尔萨尔瓦动作中无晚期 II 期和 IV 期反应，严重的心脏自主神经损伤，以及保留节后交感神经出汗功能。这些发现被解释为符合中枢自主神经衰竭。在其他 AxD 病例中报告的最常见自主症状包括便秘、尿失禁和括约肌功能障碍。据我们所知，这是 AxD 中首次进行正式自主神经测试的报告。
ANS 损伤的体征和症状可发生在 AxD 患者中，包括直立性低血压和肠道/膀胱功能障碍。我们患者的自主神经测试提示中枢自主神经通路受损。
